methyl 9-hydroxynonanoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Diethyl axodicarboxylate (1.39 g, 8 mmol) in THF (5 mL, was added dropwise to a stirred solution of methyl 9-hydroxynonanoate (1.50 g, 8 mmol), 3,4-diphenylimidazolidine-2,5-dione (2.02 g, 8 mmol) obtained according to the procedure of K. C. Joshi, et al., J. Het. Chem., 18, 1651-1653 (1981) and triphenylphosphine (2.10 g, 8 mmol) in THF (35 mL). The mixture was stirred at room temperature for 72 hours, the THF removed in vacuo and the residue triturated with a mixture of hexanes and diethyl ether. The mixture was filtered, the filtrate concentrated and subjected to chromatography on a column of silica gel using a mixture of hexanes and ethyl acetate (3:2) as eluent. Elution gave methyl 2,5-dioxo-3,4-diphenyl-1-imidazolidinenonanoate (2.78 g, 82%), mp 69°-72° C. obtained the THF removed in vacuo the residue triturated with a mixture of hexanes and diethyl ether The mixture was filtered the filtrate concentrated a mixture of hexanes and ethyl acetate (3:2) as eluent Elution

反応条件: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of methyl-9-hydroxy-nonanoate (1.1 g, 5.85 mmol, 1.0 equiv) in CH2Cl2 (30 mL, 0.2M) at 0° C. was treated successively with CBr4 (2.5 g, 7.54 mmol, 1.3 equiv) and PPh3 (2.15 g, 8.19 mmol. 1.4 equiv) and the reaction mixture was stirred at 4° C. for 10 h. The reaction mixture was then concenctrated under reduced pressure and washed repeatedly with Et2O (8×10 mL washes). The Et2O washes were combined and concentrated under reduced pressure. Chromatography (SiO2, 5 cm×15 cm, hexanes) afforded 13 as a clear, colorless oil (1.02 g, 1.47 g theorectical, 69.5%): 1H NMR (CDCl3, 250 MHz) d 3.64 (s, 3H, C(O)OCH3), 3.38 (t, 2H, J=6.8 Hz, CH2Br), 2.29 (t, 2H, J=7.4 Hz CH2C(O)OCH3), 1.83 (p, 2H, CH2CH2Br), 1.63 (m, 2H, CH2CH2C(O)OCH3) 1.47-1.28 (m, 8H, alkyl protons). washed repeatedly with Et2O (8×10 mL washes) concentrated under reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dichloromethane (20 mL) was added with methyl 9-hydroxynonanoate (2.1 g) and pyridine (1.8 g), stirred at 0° C., added with methanesulfonyl chloride (1.3 mL), gradually warmed to room temperature and stirred for one day. The reaction solution was added with water and then extracted twice with dichloromethane. The resulting organic layer was washed with 1 N hydrochloric acid and saturated sodium hydrogencarbonate solution. The organic layer was dried over anhydrous sodium sulfate, and then the solvent was removed. The resulting residue was purified by silica gel column chromatography to obtain methyl 9-(methanesulfonyloxy)nonanoate (2.1 g, yield: 68%). gradually warmed to room temperature stirred for one day extracted twice with dichloromethane The resulting organic layer was washed with 1 N hydrochloric acid and saturated sodium hydrogencarbonate solution The organic layer was dried over anhydrous sodium sulfate the solvent was removed The resulting residue was purified by silica gel column chromatography

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dichloromethane (20 mL) was added with methyl 9-hydroxynonanoate (2.1 g) and pyridine (1.8 g), stirred at 0° C., added with methanesulfonyl chloride (1.3 mL), gradually warmed to room temperature and stirred for one day. The reaction solution was added with water and then extracted twice with dichloromethane. The resulting organic layer was washed with 1 N hydrochloric acid and saturated sodium hydrogencarbonate solution. The organic layer was dried over anhydrous sodium sulfate, and then the solvent was removed. The resulting residue was purified by silica gel column chromatography to obtain methyl 9-(methanesulfonyloxy)nonanoate (2.1 g, yield: 68%). gradually warmed to room temperature stirred for one day extracted twice with dichloromethane The resulting organic layer was washed with 1 N hydrochloric acid and saturated sodium hydrogencarbonate solution The organic layer was dried over anhydrous sodium sulfate the solvent was removed The resulting residue was purified by silica gel column chromatography

反応条件: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of methyl-9-hydroxy-nonanoate (1.1 g, 5.85 mmol, 1.0 equiv) in CH2Cl2 (30 mL, 0.2 M) at 0° C. was treated successively with CBr4 (2.5 g, 7.54 mmol, 1.3 equiv) and PPh3 (2.15 g, 8.19 mmol, 1.4 equiv) and the reaction mixture was stirred at 4° C. for 10 h. The reaction mixture was then concenctrated under reduced pressure and washed repeatedly with Et2O (8×10 mL washes). The Et2O washes were combined and concentrated under reduced pressure. Chromatography (SiO2,5 cm×15 cm, hexanes) afforded the intermediate as a clear, colorless oil (1.02 g, 1.47 g theorectical, 69.5 %): 1H NMR (CDCl3,250 MHz) d 3.64 (s, 3H, C(O)OCH3), 3.38 (t, 2H, J=6.8 Hz, CH2Br), 2.29 (t, 2H, J=7.4 Hz CH2C(O)OCH3), 1.83 (p, 2H, cH2CH2Br), 1.63 (m, 2H, CH2CH2C(O)OCH3) 1.47-1.28 (m, 8H, alkyl protons). washed repeatedly with Et2O (8×10 mL washes) concentrated under reduced pressure Chromatography (SiO2,5 cm×15 cm, hexanes) afforded the intermediate as a clear, colorless oil (1.02 g, 1.47 g theorectical, 69.5 %)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of methyl-9-hydroxy-nonanoate (0.838 g, 4.46 mmol, 1.0 equiv: Aldrich) in CH2Cl2 (15 mL, 0.3 M) was treated successively with Et3N (0.75 mL, 5.38 mmol, 1.2 equiv), t-butylchlorodiphenylsilane (1.28 mL, 4.93 mmol, 1.1 equiv), and DMAP (0.180 g, 1.48 mmol, 0.33 equiv), and the reaction mixture was stirred at 25° C. for 12 h. Saturated aqueous NH4Cl was added to the reaction mixture and the mixture was partitioned between CH2Cl2 (100 mL) and H2O (100 mL). The organic layer was dried (Na2SO4) and concentrated under reduced pressure. Chromatography (SiO2, 5 cm×15 cm, 0-5% EtOAc-hexanes gradient elution ) afforded the intermeidate as a clear, colorless oil (1.22g, 1.831 theoretical, 64.1%): 1H NMR (CDCl3,250 MHz) δ 7.66 (m, 4H, ArH), 7.38 (m, 6H, ArH), 3.67-3.62 (m, 5H, C(O)OCH3 and CH2OTBDPS), 2.30 (t, 2H, J=7.4 Hz, CH2C(O)OCH3), 1.58 (m, 4H, CH2CH2OTBDPS and CH2CH2C(O)OCH3), 1.28 (b s, 8H, alkyl protons), 1.05 (s, 9H, C(CH3) 3) the mixture was partitioned between CH2Cl2 (100 mL) and H2O (100 mL) The organic layer was dried (Na2SO4) concentrated under reduced pressure Chromatography (SiO2, 5 cm×15 cm, 0-5% EtOAc-hexanes gradient elution ) afforded the intermeidate as a clear, colorless oil (1.22g, 1.831 theoretical, 64.1%)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of methyl-9-hydroxy-nonanoate (0.838 g, 4.46 mmol, 1.0 equiv: Aldrich) in CH2Cl2 (15 mL, 0.3 M) was treated successively with Et3N (0.75 mL, 5.38 mmol, 1.2 equiv), t-butylchlorodiphenylsilane (1.28 mL, 4.93 mmol, 1.1 equiv), and DMAP (0.180 g, 1.48 mmol, 0.33 equiv), and the reaction mixture was stirred at 25° C. for 12 h. Saturated aqueous NH4Cl was added to the reaction mixture and the mixture was partitioned between CH2Cl2 (100 mL) and H2O (100 mL). The organic layer was dried (Na2SO4) and concentrated under reduced pressure. Chromatography (SiO2, 5 cm×15 cm, 0-5% EtOAc-hexanes gradient elution ) afforded the intermeidate as a clear, colorless oil (1.22g, 1.831 theoretical, 64.1%): 1H NMR (CDCl3,250 MHz) δ 7.66 (m, 4H, ArH), 7.38 (m, 6H, ArH), 3.67-3.62 (m, 5H, C(O)OCH3 and CH2OTBDPS), 2.30 (t, 2H, J=7.4 Hz, CH2C(O)OCH3), 1.58 (m, 4H, CH2CH2OTBDPS and CH2CH2C(O)OCH3), 1.28 (b s, 8H, alkyl protons), 1.05 (s, 9H, C(CH3) 3) the mixture was partitioned between CH2Cl2 (100 mL) and H2O (100 mL) The organic layer was dried (Na2SO4) concentrated under reduced pressure Chromatography (SiO2, 5 cm×15 cm, 0-5% EtOAc-hexanes gradient elution ) afforded the intermeidate as a clear, colorless oil (1.22g, 1.831 theoretical, 64.1%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of nonanedioic acid monomethyl ester (4.80 g, 20 mmol) in THF (20 mL) at −20° C. was added a solution of borane-dimethylsulfide in THF (2.0 M, 10 mL) over 10 min. The resulting mixture was stirred for an additional 10 min, and then allowed to stir at room temperature overnight. Aqueous K2CO3 solution was added, and the product was extracted with ethyl ether (3×). The crude product was purified by flash column chromatography (hexane/EtOAc:2/1) to yield 9-hydroxy-nonanoic acid methyl ester 4-B (2.0 g, 55%). to stir at room temperature overnight the product was extracted with ethyl ether (3×) The crude product was purified by flash column chromatography (hexane/EtOAc:2/1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of nonanedioic acid monomethyl ester (4.80 g, 20 mmol) in THF (20 mL) at −20° C. was added a solution of borane-dimethylsulfide in THF (2.0 M, 10 mL) over 10 min. The resulting mixture was stirred for an additional 10 min, and then allowed to stir at room temperature overnight. Aqueous K2CO3 solution was added, and the product was extracted with ethyl ether (3×). The crude product was purified by flash column chromatography (hexane/EtOAc:2/1) to yield 9-hydroxy-nonanoic acid methyl ester 4-B (2.0 g, 55%). to stir at room temperature overnight the product was extracted with ethyl ether (3×) The crude product was purified by flash column chromatography (hexane/EtOAc:2/1)