Synthesis and Structure-Affinity Relationships of Receptor Ligands with 1,3-Dioxane Structure methods
Show snapshot details
On this page
This experiment, in seven questions
Jump straight to the part of the recipe you need. Data and provenance labels stay close to the action they support.
Shopping and prep list
What do I need before I start?
Biological model pending
Subject model for the experiment.
- Use
- confirm full cohort details in the source paper
Before you run
What should be confirmed before execution?
First confirmation
Species or subject information is missing.
Confirm before execution
Protocol does not list structured equipment.
Confirm before execution
This page shows passages quoted from the paper. Equipment, materials, times, and temperatures are hidden until the page is rebuilt from the full paper and checked by a reviewer. Check the paper before using this method.
Confirm before execution
Open the source paper before finalizing run-specific details.
Procurement checkpoint
Use source-stated vendors where present. Treat mapped products as sourcing options unless the page marks an exact source match.
Open quote workflowStep-by-step procedure
What do I do, in order?
2.3. Lipophilicity and Metabolic Stability (In Vitro) of Selected σ 1 Receptor Ligands
A balanced lipophilicity is crucial for the pharmacokinetics and pharmacodynamics of drugs. As measure for the lipophilicity, the logD 7.4 value of selected compounds was recorded using the recently developed micro-shake flask method. In this method, a compound was distributed between a MOPS buffer pH 7.4 and n -octanol and the amount of compound in the buffer layer was determined by MS analysis [ ] ( ).
3. Materials and Materials
Pentane-1,3,5-triol ( 6, 1.69 g, 14 mmol), benzaldehyde ( 7a, 3.5 mL, 35 mmol) and p -toluenesulfonic acid (75 mg) were dissolved in CH 2 Cl 2 abs. (60 mL) and heated to reflux for 16 h, using an inverse Dean-Stark apparatus. For workup, the reaction mixture was washed with saturated aqueous solution of NaHCO 3 (3 × 20 mL), dried (K 2 CO 3 ) and the solvent was removed in vacuo. The residue was purified by flash column chromatography (Ø 6 cm, cyclohexane:thyl acetate = 1:1, length 20 cm, fraction 65 mL, R f = 0.28). Colorless oil, yield 2.27 g (78%). C 12 H 16 O 3, M r = 208.3. MS (EI): m / z [%] = 208 (M, 33), 207 (M-H, 100), 177 (M-CH 2 OH, 13), 105 (PhCO, 47), 77 (Ph, 42). IR (neat): ν ˜ [cm -1 ] = 3420 (O-H), 3066, 3034 (Ar-H), 2947, 2857 (C-H), 1098 (C-O-C), 749, 697 (arom. monosubst.). 1 H NMR (CDCl 3 ): δ [ppm] = 1.54 (dtd, J = 13.1/2.5/1.4 Hz,...
3. Materials and Materials
( Z )- 10a (R f = 0.15): Colorless oil, yield 76 mg (9.1%). C 16 H 20 O 4, M r = 276.3. IR (neat): ν ˜ [cm -1 ] = 2977, 2922, 2851 (C-H), 1714 (CO 2 R), 1646 (C=C), 1098 (C-O), 750, 697 (arom. monosubst). 1 H NMR (CDCl 3 ): δ [ppm] = 1.29 (t, J = 7.1 Hz, 3 H, CO 2 CH 2 C H 3 ), 1.56 (dtd, J = 13.3/3.8/1.4 Hz, 1 H, 5-H eq ), 1.89 (dddd, J = 13.1/12.3/11.4/5.1 Hz, 1 H, 5-H ax ), 2.87-2.95 (m, 1 H, diox-C H 2 -CH=CH), 3.10 (dddd, J = 15.7/7.6/4.5/1.7 Hz, 1 H, diox-C H 2 -CH=CH), 3.97 (ddd, J = 12.3/11.6/2.6 Hz, 1 H, 6-H ax ), 3.96-4.02 (m, 1 H, 4-H ax ), 4.18 (q, J = 7.1 Hz, 2 H, CO 2 C H 2 CH 3 ), 4.27 (ddd, J = 11.3/4.9/1.1 Hz, 1 H, 6-H eq ), 5.52 (s, 1 H, 2-H ax ), 5.88 (dt, J = 11.6/1.8 Hz, 1 H, CH=C H -CO 2 R), 6.45 (ddd, J = 11.6/7.7/6.9 Hz, 1 H, C H =CH-CO 2 R), 7.31-7.39 (m, 3 H, Ar-H), 7.48-7.50 (m, 2 H, Ar-H). HPLC (method ACN): pur...
3. Materials and Materials
Pentane-1,3,5-triol ( 6, 2.01 g, 16.6 mmol), propiophenone ( 7b 4.4 mL, 33.2 mmol) and p -toluenesulfonic acid (75 mg) were dissolved in toluene (90 mL) and heated to reflux for 1.5 h, using a Dean-Stark apparatus filled with molecular sieves 4 Å. For workup, the reaction mixture was washed with saturated aqueous solution of NaHCO 3 (3 × 30 mL) and with brine (1 × 30 mL) and dried (K 2 CO 3 ). The solvent was removed in vacuo, and the residue was purified by flash column chromatography (Ø 8 cm, cyclohexane:ethyl acetate = 7:3, length 17 cm, fraction 65 mL, R f = 0.24). Colorless oil, yield 3.51 g (90%). C 14 H 20 O 3, M r = 236.3. MS (EI): m / z [%] = 237 (M + H, 24), 207 (M-CH 3 -CH 2, 100), 105 (Ph-CO, 67). IR (neat): ν ˜ [cm -1 ] = 3420 (O-H), 2926, 2875 (C-H), 756, 703 (arom. monosubst.). 1 H NMR (CDCl 3 ): δ [ppm] = 0.80 (t, J = 7.5 Hz,...
3. Materials and Materials
Under N 2 atmosphere, oxalyl chloride (0.51 mL, 6 mmol) was dissolved in CH 2 Cl 2 abs. (25 mL) and cooled down to -78 °C. At this temperature, a solution of DMSO (0.85 mL, 12 mmol) in CH 2 Cl 2 abs. (7.5 mL) was added very slowly (using a syringe pump, 7 mL/h) and the mixture was stirred for 15 min at -78 °C. Then, a solution of the alcohol 8a (1.043 g, 5 mmol) in CH 2 Cl 2 abs. (7.5 mL) was added (using a syringe pump, 12 mL/h). The mixture was stirred for additional 45 min at -78 °C before NEt 3 (3.5 mL, 25 mmol) was added. After warming to rt, n -hexane (40 mL) was added. The precipitate was filtered off using a glass suction filter and washed several times with Et 2 O. The filtrate was concentrated (600 mbar, 40 °C) and the filtration procedure was repeated once. The solvent was removed in vacuo, and the residue was purified by flash column c...
3. Materials and Materials
Under N 2 atmosphere, oxalyl chloride (0.87 mL, 10.15 mmol) was dissolved in CH 2 Cl 2 abs. (26 mL) and cooled down to -78 °C. At this temperature, a solution of DMSO (1.44 mL, 20.30 mmol) in CH 2 Cl 2 abs. (12 mL) was added very slowly (using a syringe pump, 9 mL/h) and the mixture was stirred for 15 min at -78 °C. Then a solution of the alcohol 8b (2.00 g, 8.46 mmol) in CH 2 Cl 2 abs. (12 mL) was added (using a syringe pump, 18 mL/h). The mixture was stirred for additional 45 min at -78 °C before NEt 3 (6.6 mL, 42.30 mmol) was added. After warming to rt, n -hexane (40 mL) was added. The precipitate was filtered off using a glass suction filter and washed several times with Et 2 O. The filtrate was concentrated (600 mbar, 40 °C) and the filtration procedure was repeated once. The solvent was removed in vacuo, and the residue was purified by flash...
3. Materials and Materials
Under N 2 atmosphere the commercially available P-ylide Ph 3 P=CH-CO 2 Et (1.23 g, 4.5 mmol) was dissolved in THF abs. (20 mL). A solution of the aldehyde 9a (619 mg, 3 mmol) in THF abs. (8 mL) was added, and the solution was diluted with THF to a total volume of 40 mL. The mixture was stirred for 24 h at rt and then heated to reflux for 2 h. Water (30 mL) and brine (15 mL) were added, and the mixture was extracted with ethyl acetate (3 × 30 mL). The combined organic layers were washed with brine (1 × 40 mL) and dried (K 2 CO 3 ). The solvent was removed in vacuo, and the residue was adsorbed on silica gel and loaded on the column (Ø 5.5 cm, cyclohexane:ethyl acetate = 9:1, length 18 cm, fraction 65 mL).
3. Materials and Materials
( E )- 10a (R f = 0.12: Colorless oil, yield 712 mg (86%). C 16 H 20 O 4, M r = 276.3. MS (ESI): m / z [%] = 277 (M + H, 10), 294 (M + NH 4, 22), 299 (M + Na, 26), 575 (2 × M + Na, 20), 577 (M + Ph 3 P = O + Na, 100). IR (neat): ν ˜ [cm -1 ] = 2979, 2853 (C-H), 1715 (CO 2 R), 1656 (C=C), 1099 (C-O), 751, 697 (arom. monosubst). 1H NMR (CDCl 3 ): δ [ppm] = 1.29 (t, J = 7.1 Hz, 3 H, CO 2 CH 2 -C H 3 ), 1.53-1.58 (m, 1 H, 5-H eq ), 1.85 (dddd, J = 13.1/12.3/11.4/5.0 Hz, 1 H, 5-H ax ), 2.46 (dddd, J = 14.7/7.4/5.7/1.4 Hz, 1 H, diox-C H 2 -CH=CH), 1.60 (dtd, J = 14.8/6.9/1.5 Hz, 1 H, diox-C H 2 -CH=CH), 3.96 (td, J = 12.0/2.6 Hz, 1 H, 6-H ax ), 3.95-4.02 (m, 1 H, 4-H ax ), 4.19 (q, J = 7.1 Hz, 2 H, CO 2 C H 2 -CH 3 ), 4.28 (ddd, J = 11.4/5.0/1.2 Hz, 1 H, 6-H eq ), 5.52 (s, 1 H, 2-H ax ), 5.93 (dt, J = 15.7/1.4 Hz, 1 H, CH=C H -CO 2 R), 7.01 (dt, J = 1...
Measurement outputs
What raw and processed outputs should exist?
Analysis plan
How should the outputs become interpretable results?
Acquisition
Collect raw experimental outputs with enough metadata to preserve sample identity, condition, and timing.
inferred from protocolPreprocessing / cleaning
Review raw outputs for quality, remove unusable captures, and organize the data into a comparison-ready table or image set.
inferred from protocolScoring or quantification
Quantify the primary endpoint described in the methods before moving into any statistical comparison.
inferred from protocolStatistical comparison
Statistical method not yet structured for this page.
inferred from protocolReporting output
Report representative outputs alongside the summary comparison used to support the conclusion.
inferred from protocolSource and audit
What supports the facts on this page?
Evidence quotes (8)
A balanced lipophilicity is crucial for the pharmacokinetics and pharmacodynamics of drugs. As measure for the lipophilicity, the logD 7.4 value of selected compounds was recorded using the recently developed micro-shake flask method. In this method, a compound was distributed between a MOPS buffer pH 7.4 and n -octanol and the amount of compound in the buffer layer was determined by MS analysis [ ] ( ).
Pentane-1,3,5-triol ( 6, 1.69 g, 14 mmol), benzaldehyde ( 7a, 3.5 mL, 35 mmol) and p -toluenesulfonic acid (75 mg) were dissolved in CH 2 Cl 2 abs. (60 mL) and heated to reflux for 16 h, using an inverse Dean-Stark apparatus. For workup, the reaction mixture was washed with saturated aqueous solution of NaHCO 3 (3 × 20 mL), dried (K 2 CO 3 ) and the solvent was removed in vacuo. The residue was purified by flash column chromatography (Ø 6 cm, cyclohexane:thyl acetate = 1:1, length 20 cm, fraction 65 mL, R f = 0.28). Colorless oil, yield 2.27 g (78%). C 12 H 16 O 3, M r = 208.3. MS (EI): m / z [%] = 208 (M, 33), 207 (M-H, 100), 177 (M-CH 2 OH, 13), 105 (PhCO, 47), 77 (Ph, 42). IR (neat): ν ˜ [cm -1 ] = 3420 (O-H), 3066, 3034 (Ar-H), 2947, 2857 (C-H), 1098 (C-O-C), 749, 697 (arom. monosubst.). 1 H NMR (CDCl 3 ): δ [ppm] = 1.54 (dtd, J = 13.1/2.5/1.4 Hz, 1H, 5-H eq ), 1.79-1.99 (m, 3H, C H 2 -CH 2 -OH and 5-H ax ), 2.11 (dd, J = 6.1/4.7 Hz, 1H, CH 2 -O H ), 3.79-3.90 (m, 2H, C H 2 -OH), 3.99 (td, J = 11.7/2.6 Hz, 1H, 6-H ax ), 4.09-4.16 (m, 1H, 4-H ax ), 4.28 (ddd, J = 11.4/5.0/1.1 Hz, 1H, 6-H eq ), 5.54 (s, 1H, 2-H ax ), 7.30R...
( Z )- 10a (R f = 0.15): Colorless oil, yield 76 mg (9.1%). C 16 H 20 O 4, M r = 276.3. IR (neat): ν ˜ [cm -1 ] = 2977, 2922, 2851 (C-H), 1714 (CO 2 R), 1646 (C=C), 1098 (C-O), 750, 697 (arom. monosubst). 1 H NMR (CDCl 3 ): δ [ppm] = 1.29 (t, J = 7.1 Hz, 3 H, CO 2 CH 2 C H 3 ), 1.56 (dtd, J = 13.3/3.8/1.4 Hz, 1 H, 5-H eq ), 1.89 (dddd, J = 13.1/12.3/11.4/5.1 Hz, 1 H, 5-H ax ), 2.87-2.95 (m, 1 H, diox-C H 2 -CH=CH), 3.10 (dddd, J = 15.7/7.6/4.5/1.7 Hz, 1 H, diox-C H 2 -CH=CH), 3.97 (ddd, J = 12.3/11.6/2.6 Hz, 1 H, 6-H ax ), 3.96-4.02 (m, 1 H, 4-H ax ), 4.18 (q, J = 7.1 Hz, 2 H, CO 2 C H 2 CH 3 ), 4.27 (ddd, J = 11.3/4.9/1.1 Hz, 1 H, 6-H eq ), 5.52 (s, 1 H, 2-H ax ), 5.88 (dt, J = 11.6/1.8 Hz, 1 H, CH=C H -CO 2 R), 6.45 (ddd, J = 11.6/7.7/6.9 Hz, 1 H, C H =CH-CO 2 R), 7.31-7.39 (m, 3 H, Ar-H), 7.48-7.50 (m, 2 H, Ar-H). HPLC (method ACN): purity 93.0%, t R = 20.90 min. Contamination with 2.9% of ( E )- 10a (t R = 20.35 min) was observed.
Pentane-1,3,5-triol ( 6, 2.01 g, 16.6 mmol), propiophenone ( 7b 4.4 mL, 33.2 mmol) and p -toluenesulfonic acid (75 mg) were dissolved in toluene (90 mL) and heated to reflux for 1.5 h, using a Dean-Stark apparatus filled with molecular sieves 4 Å. For workup, the reaction mixture was washed with saturated aqueous solution of NaHCO 3 (3 × 30 mL) and with brine (1 × 30 mL) and dried (K 2 CO 3 ). The solvent was removed in vacuo, and the residue was purified by flash column chromatography (Ø 8 cm, cyclohexane:ethyl acetate = 7:3, length 17 cm, fraction 65 mL, R f = 0.24). Colorless oil, yield 3.51 g (90%). C 14 H 20 O 3, M r = 236.3. MS (EI): m / z [%] = 237 (M + H, 24), 207 (M-CH 3 -CH 2, 100), 105 (Ph-CO, 67). IR (neat): ν ˜ [cm -1 ] = 3420 (O-H), 2926, 2875 (C-H), 756, 703 (arom. monosubst.). 1 H NMR (CDCl 3 ): δ [ppm] = 0.80 (t, J = 7.5 Hz, 3 H, diox-CH 2 -C H 3 ), 1.25-1.30 (m, 1 H, 5-H eq ), 1.69-1.89 (m, 3 H, 5-H ax, C H 2 -CH 2 -OH), 1.75 (q, J = 7.5 Hz, 2 H, diox-C H 2 -CH 3 ), 2.58 (s, 1 H, O- H ), 3.81 (td, J = 12.0/2.5 Hz, 1 H, 6-H ax ), 3.87-3.91 (m, 3 H, 6-H eq, C H 2 -OH), 3.93-4.00 (m, 1 H, 4-H ax...
Under N 2 atmosphere, oxalyl chloride (0.51 mL, 6 mmol) was dissolved in CH 2 Cl 2 abs. (25 mL) and cooled down to -78 °C. At this temperature, a solution of DMSO (0.85 mL, 12 mmol) in CH 2 Cl 2 abs. (7.5 mL) was added very slowly (using a syringe pump, 7 mL/h) and the mixture was stirred for 15 min at -78 °C. Then, a solution of the alcohol 8a (1.043 g, 5 mmol) in CH 2 Cl 2 abs. (7.5 mL) was added (using a syringe pump, 12 mL/h). The mixture was stirred for additional 45 min at -78 °C before NEt 3 (3.5 mL, 25 mmol) was added. After warming to rt, n -hexane (40 mL) was added. The precipitate was filtered off using a glass suction filter and washed several times with Et 2 O. The filtrate was concentrated (600 mbar, 40 °C) and the filtration procedure was repeated once. The solvent was removed in vacuo, and the residue was purified by flash column chromatography (Ø 5.5 cm, cyclohexane:ethyl acetate = 8:2, length 20 cm, fraction 65 mL, R f = 0.16). Colorless oil with sweet smell, yield 0.994 g (91%). C 12 H 14 O 3, M r = 206.3. MS (EI): m / z = 207 (M + H, 53), 205 (M-H, 76), 177 (M-CHO, 6), 105 (PhCO, 100), 77 (Ph, 81). IR (neat): ν...
Under N 2 atmosphere, oxalyl chloride (0.87 mL, 10.15 mmol) was dissolved in CH 2 Cl 2 abs. (26 mL) and cooled down to -78 °C. At this temperature, a solution of DMSO (1.44 mL, 20.30 mmol) in CH 2 Cl 2 abs. (12 mL) was added very slowly (using a syringe pump, 9 mL/h) and the mixture was stirred for 15 min at -78 °C. Then a solution of the alcohol 8b (2.00 g, 8.46 mmol) in CH 2 Cl 2 abs. (12 mL) was added (using a syringe pump, 18 mL/h). The mixture was stirred for additional 45 min at -78 °C before NEt 3 (6.6 mL, 42.30 mmol) was added. After warming to rt, n -hexane (40 mL) was added. The precipitate was filtered off using a glass suction filter and washed several times with Et 2 O. The filtrate was concentrated (600 mbar, 40 °C) and the filtration procedure was repeated once. The solvent was removed in vacuo, and the residue was purified by flash column chromatography (6 cm, cyclohexane:ethyl acetate = 9.25:0.75, length 18 cm, fraction 65 mL, R f = 0.09). Colorless solid, mp 55.8 °C, yield 1.76 g (89%). C 14 H 18 O 3, M r = 234.3. MS (EI): m / z [%] = 235 (M + H, 41), 205 (M-CH 3 -CH 2, 100), 105 (Ph-CO, 52). IR (neat): ν ˜...
Under N 2 atmosphere the commercially available P-ylide Ph 3 P=CH-CO 2 Et (1.23 g, 4.5 mmol) was dissolved in THF abs. (20 mL). A solution of the aldehyde 9a (619 mg, 3 mmol) in THF abs. (8 mL) was added, and the solution was diluted with THF to a total volume of 40 mL. The mixture was stirred for 24 h at rt and then heated to reflux for 2 h. Water (30 mL) and brine (15 mL) were added, and the mixture was extracted with ethyl acetate (3 × 30 mL). The combined organic layers were washed with brine (1 × 40 mL) and dried (K 2 CO 3 ). The solvent was removed in vacuo, and the residue was adsorbed on silica gel and loaded on the column (Ø 5.5 cm, cyclohexane:ethyl acetate = 9:1, length 18 cm, fraction 65 mL).
( E )- 10a (R f = 0.12: Colorless oil, yield 712 mg (86%). C 16 H 20 O 4, M r = 276.3. MS (ESI): m / z [%] = 277 (M + H, 10), 294 (M + NH 4, 22), 299 (M + Na, 26), 575 (2 × M + Na, 20), 577 (M + Ph 3 P = O + Na, 100). IR (neat): ν ˜ [cm -1 ] = 2979, 2853 (C-H), 1715 (CO 2 R), 1656 (C=C), 1099 (C-O), 751, 697 (arom. monosubst). 1H NMR (CDCl 3 ): δ [ppm] = 1.29 (t, J = 7.1 Hz, 3 H, CO 2 CH 2 -C H 3 ), 1.53-1.58 (m, 1 H, 5-H eq ), 1.85 (dddd, J = 13.1/12.3/11.4/5.0 Hz, 1 H, 5-H ax ), 2.46 (dddd, J = 14.7/7.4/5.7/1.4 Hz, 1 H, diox-C H 2 -CH=CH), 1.60 (dtd, J = 14.8/6.9/1.5 Hz, 1 H, diox-C H 2 -CH=CH), 3.96 (td, J = 12.0/2.6 Hz, 1 H, 6-H ax ), 3.95-4.02 (m, 1 H, 4-H ax ), 4.19 (q, J = 7.1 Hz, 2 H, CO 2 C H 2 -CH 3 ), 4.28 (ddd, J = 11.4/5.0/1.2 Hz, 1 H, 6-H eq ), 5.52 (s, 1 H, 2-H ax ), 5.93 (dt, J = 15.7/1.4 Hz, 1 H, CH=C H -CO 2 R), 7.01 (dt, J = 15.6/7.3 Hz, 1 H, C H =CH-CO 2 R), 7.33-7.39 (m, 3 H, Ar-H), 7.48-7.50 (m, 2 H, Ar-H). HPLC (method ACN): purity 93.4%, t R = 20.34 min. Contamination with 1.7% of ( Z )- 10a (t R = 20.35 min) was observed.
Machine-readable layer
[
{
"@context": "https://schema.org",
"@type": "HowTo",
"name": "Synthesis and Structure-Affinity Relationships of Receptor Ligands with 1,3-Dioxane Structure methods",
"description": "Protocol for Synthesis and Structure-Affinity Relationships of Receptor Ligands with 1,3-Dioxane Structure methods",
"step": [
{
"@type": "HowToStep",
"position": 1,
"name": "2.3. Lipophilicity and Metabolic Stability (In Vitro) of Selected σ 1 Receptor Ligands",
"text": "A balanced lipophilicity is crucial for the pharmacokinetics and pharmacodynamics of drugs. As measure for the lipophilicity, the logD 7.4 value of selected compounds was recorded using the recently developed micro-shake flask method. In this method, a compound was distributed between a MOPS buffer pH 7.4 and n -octanol and the amount of compound in the buffer layer was determined by MS analysis [ ] ( )."
},
{
"@type": "HowToStep",
"position": 2,
"name": "3. Materials and Materials",
"text": "Pentane-1,3,5-triol ( 6, 1.69 g, 14 mmol), benzaldehyde ( 7a, 3.5 mL, 35 mmol) and p -toluenesulfonic acid (75 mg) were dissolved in CH 2 Cl 2 abs. (60 mL) and heated to reflux for 16 h, using an inverse Dean-Stark apparatus. For workup, the reaction mixture was washed with saturated aqueous solution of NaHCO 3 (3 × 20 mL), dried (K 2 CO 3 ) and the solvent was removed in vacuo. The residue was purified by flash column chromatography (Ø 6 cm, cyclohexane:thyl acetate = 1:1, length 20 cm, fraction 65 mL, R f = 0.28). Colorless oil, yield 2.27 g (78%). C 12 H 16 O 3, M r = 208.3. MS (EI): m / z [%] = 208 (M, 33), 207 (M-H, 100), 177 (M-CH 2 OH, 13), 105 (PhCO, 47), 77 (Ph, 42). IR (neat): ν ˜ [cm -1 ] = 3420 (O-H), 3066, 3034 (Ar-H), 2947, 2857 (C-H), 1098 (C-O-C), 749, 697 (arom. monosubst.). 1 H NMR (CDCl 3 ): δ [ppm] = 1.54 (dtd, J = 13.1/2.5/1.4 Hz,..."
},
{
"@type": "HowToStep",
"position": 3,
"name": "3. Materials and Materials",
"text": "( Z )- 10a (R f = 0.15): Colorless oil, yield 76 mg (9.1%). C 16 H 20 O 4, M r = 276.3. IR (neat): ν ˜ [cm -1 ] = 2977, 2922, 2851 (C-H), 1714 (CO 2 R), 1646 (C=C), 1098 (C-O), 750, 697 (arom. monosubst). 1 H NMR (CDCl 3 ): δ [ppm] = 1.29 (t, J = 7.1 Hz, 3 H, CO 2 CH 2 C H 3 ), 1.56 (dtd, J = 13.3/3.8/1.4 Hz, 1 H, 5-H eq ), 1.89 (dddd, J = 13.1/12.3/11.4/5.1 Hz, 1 H, 5-H ax ), 2.87-2.95 (m, 1 H, diox-C H 2 -CH=CH), 3.10 (dddd, J = 15.7/7.6/4.5/1.7 Hz, 1 H, diox-C H 2 -CH=CH), 3.97 (ddd, J = 12.3/11.6/2.6 Hz, 1 H, 6-H ax ), 3.96-4.02 (m, 1 H, 4-H ax ), 4.18 (q, J = 7.1 Hz, 2 H, CO 2 C H 2 CH 3 ), 4.27 (ddd, J = 11.3/4.9/1.1 Hz, 1 H, 6-H eq ), 5.52 (s, 1 H, 2-H ax ), 5.88 (dt, J = 11.6/1.8 Hz, 1 H, CH=C H -CO 2 R), 6.45 (ddd, J = 11.6/7.7/6.9 Hz, 1 H, C H =CH-CO 2 R), 7.31-7.39 (m, 3 H, Ar-H), 7.48-7.50 (m, 2 H, Ar-H). HPLC (method ACN): pur..."
},
{
"@type": "HowToStep",
"position": 4,
"name": "3. Materials and Materials",
"text": "Pentane-1,3,5-triol ( 6, 2.01 g, 16.6 mmol), propiophenone ( 7b 4.4 mL, 33.2 mmol) and p -toluenesulfonic acid (75 mg) were dissolved in toluene (90 mL) and heated to reflux for 1.5 h, using a Dean-Stark apparatus filled with molecular sieves 4 Å. For workup, the reaction mixture was washed with saturated aqueous solution of NaHCO 3 (3 × 30 mL) and with brine (1 × 30 mL) and dried (K 2 CO 3 ). The solvent was removed in vacuo, and the residue was purified by flash column chromatography (Ø 8 cm, cyclohexane:ethyl acetate = 7:3, length 17 cm, fraction 65 mL, R f = 0.24). Colorless oil, yield 3.51 g (90%). C 14 H 20 O 3, M r = 236.3. MS (EI): m / z [%] = 237 (M + H, 24), 207 (M-CH 3 -CH 2, 100), 105 (Ph-CO, 67). IR (neat): ν ˜ [cm -1 ] = 3420 (O-H), 2926, 2875 (C-H), 756, 703 (arom. monosubst.). 1 H NMR (CDCl 3 ): δ [ppm] = 0.80 (t, J = 7.5 Hz,..."
},
{
"@type": "HowToStep",
"position": 5,
"name": "3. Materials and Materials",
"text": "Under N 2 atmosphere, oxalyl chloride (0.51 mL, 6 mmol) was dissolved in CH 2 Cl 2 abs. (25 mL) and cooled down to -78 °C. At this temperature, a solution of DMSO (0.85 mL, 12 mmol) in CH 2 Cl 2 abs. (7.5 mL) was added very slowly (using a syringe pump, 7 mL/h) and the mixture was stirred for 15 min at -78 °C. Then, a solution of the alcohol 8a (1.043 g, 5 mmol) in CH 2 Cl 2 abs. (7.5 mL) was added (using a syringe pump, 12 mL/h). The mixture was stirred for additional 45 min at -78 °C before NEt 3 (3.5 mL, 25 mmol) was added. After warming to rt, n -hexane (40 mL) was added. The precipitate was filtered off using a glass suction filter and washed several times with Et 2 O. The filtrate was concentrated (600 mbar, 40 °C) and the filtration procedure was repeated once. The solvent was removed in vacuo, and the residue was purified by flash column c..."
},
{
"@type": "HowToStep",
"position": 6,
"name": "3. Materials and Materials",
"text": "Under N 2 atmosphere, oxalyl chloride (0.87 mL, 10.15 mmol) was dissolved in CH 2 Cl 2 abs. (26 mL) and cooled down to -78 °C. At this temperature, a solution of DMSO (1.44 mL, 20.30 mmol) in CH 2 Cl 2 abs. (12 mL) was added very slowly (using a syringe pump, 9 mL/h) and the mixture was stirred for 15 min at -78 °C. Then a solution of the alcohol 8b (2.00 g, 8.46 mmol) in CH 2 Cl 2 abs. (12 mL) was added (using a syringe pump, 18 mL/h). The mixture was stirred for additional 45 min at -78 °C before NEt 3 (6.6 mL, 42.30 mmol) was added. After warming to rt, n -hexane (40 mL) was added. The precipitate was filtered off using a glass suction filter and washed several times with Et 2 O. The filtrate was concentrated (600 mbar, 40 °C) and the filtration procedure was repeated once. The solvent was removed in vacuo, and the residue was purified by flash..."
},
{
"@type": "HowToStep",
"position": 7,
"name": "3. Materials and Materials",
"text": "Under N 2 atmosphere the commercially available P-ylide Ph 3 P=CH-CO 2 Et (1.23 g, 4.5 mmol) was dissolved in THF abs. (20 mL). A solution of the aldehyde 9a (619 mg, 3 mmol) in THF abs. (8 mL) was added, and the solution was diluted with THF to a total volume of 40 mL. The mixture was stirred for 24 h at rt and then heated to reflux for 2 h. Water (30 mL) and brine (15 mL) were added, and the mixture was extracted with ethyl acetate (3 × 30 mL). The combined organic layers were washed with brine (1 × 40 mL) and dried (K 2 CO 3 ). The solvent was removed in vacuo, and the residue was adsorbed on silica gel and loaded on the column (Ø 5.5 cm, cyclohexane:ethyl acetate = 9:1, length 18 cm, fraction 65 mL)."
},
{
"@type": "HowToStep",
"position": 8,
"name": "3. Materials and Materials",
"text": "( E )- 10a (R f = 0.12: Colorless oil, yield 712 mg (86%). C 16 H 20 O 4, M r = 276.3. MS (ESI): m / z [%] = 277 (M + H, 10), 294 (M + NH 4, 22), 299 (M + Na, 26), 575 (2 × M + Na, 20), 577 (M + Ph 3 P = O + Na, 100). IR (neat): ν ˜ [cm -1 ] = 2979, 2853 (C-H), 1715 (CO 2 R), 1656 (C=C), 1099 (C-O), 751, 697 (arom. monosubst). 1H NMR (CDCl 3 ): δ [ppm] = 1.29 (t, J = 7.1 Hz, 3 H, CO 2 CH 2 -C H 3 ), 1.53-1.58 (m, 1 H, 5-H eq ), 1.85 (dddd, J = 13.1/12.3/11.4/5.0 Hz, 1 H, 5-H ax ), 2.46 (dddd, J = 14.7/7.4/5.7/1.4 Hz, 1 H, diox-C H 2 -CH=CH), 1.60 (dtd, J = 14.8/6.9/1.5 Hz, 1 H, diox-C H 2 -CH=CH), 3.96 (td, J = 12.0/2.6 Hz, 1 H, 6-H ax ), 3.95-4.02 (m, 1 H, 4-H ax ), 4.19 (q, J = 7.1 Hz, 2 H, CO 2 C H 2 -CH 3 ), 4.28 (ddd, J = 11.4/5.0/1.2 Hz, 1 H, 6-H eq ), 5.52 (s, 1 H, 2-H ax ), 5.93 (dt, J = 15.7/1.4 Hz, 1 H, CH=C H -CO 2 R), 7.01 (dt, J = 1..."
}
],
"tool": [],
"supply": [],
"isBasedOn": {
"@type": "ScholarlyArticle",
"headline": "Synthesis and Structure-Affinity Relationships of Receptor Ligands with 1,3-Dioxane Structure",
"datePublished": "2025",
"author": [
{
"@type": "Person",
"name": "Elisabeth Quick"
},
{
"@type": "Person",
"name": "Dirk Schepmann"
},
{
"@type": "Person",
"name": "Bernhard Wünsch"
}
],
"identifier": "10.1016/S0022-3565(25)30536-7"
}
},
{
"@context": "https://schema.org",
"@type": "BreadcrumbList",
"itemListElement": [
{
"@type": "ListItem",
"position": 1,
"name": "Experiments",
"item": "https://replicatescience.com/experiments"
},
{
"@type": "ListItem",
"position": 2,
"name": "Synthesis and Structure-Affinity Relationships of Receptor Ligands with 1,3-Dioxane Structure methods",
"item": "https://replicatescience.com/experiments/synthesis-and-structure-affinity-relationships-of-receptor-ligands-with-1-3-dioxane-structure-methods-elisabeth-quick-pmc12865480/synthesis-and-structure-affinity-relationships-of-receptor-ligands-with-13-dioxa"
}
]
}
]