2-cyclopentyl-N-methoxy-N-methylacetamide

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

実験手順: A solution of 2.0 mL (15.9 mmol) of cyclopentylacetic acid in 80 mL of CH2Cl2 at 0° C. was treated with 3.7 mL (33.6 mmol) of N-methyl-morpholine and 2.2 mL (16.9 mmol) of isobutyl chloroformate. After stirring for 20 min, 1.61 g (16.5 mmol) of N,O-dimethyl-hydroxylamine.HCl was added. The reaction was warmed to rt and stirred for 3 h. The reaction was partitioned between 200 mL of EtOAc and 200 mL 2.0 N HCl. After separating the phases, the organic layer was washed with 200 mL of 1.0 N NaHCO3, dried over Na2SO4 and concentrated. Flash chromatography on silica gel using 4:1 v/v hexanes/EtOAc afforded 2.28 g (83%) of the title compound as a colorless oil. RF: 0.27 (4:1 v/v hexanes/ EtOAc). 1H NMR (300 MHz): δ 1.12-1.23 (m, 2H), 1.51-1.89 (m, 6H), 2.28 (m, 1H), 2.44 (d, J=7.5, 2H), 3.18 (s, 3H), 3.67 (s, 3H). stirred for 3 h The reaction was partitioned between 200 mL of EtOAc and 200 mL 2.0 N HCl After separating the phases the organic layer was washed with 200 mL of 1.0 N NaHCO3 dried over Na2SO4 concentrated

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

実験手順: A solution of 2.0 mL (15.9 mmol) of cyclopentylacetic acid in 80 mL of CH2Cl2 at 0° C. was treated with 3.7 mL (33.6 mmol) of N-methyl-morpholine and 2.2 mL (16.9 mmol) of isobutyl chloroformate. After stirring for 20 min, 1.61 g (16.5 mmol) of N,O-dimethyl-hydroxylamine.HCl was added. The reaction was warmed to rt and stirred for 3 h. The reaction was partitioned between 200 mL of EtOAc and 200 mL 2.0 N HCl. After separating the phases, the organic layer was washed with 200 mL of 1.0 N NaHCO3, dried over Na2SO4 and concentrated. Flash chromatography on silica gel using 4:1 v/v hexanes/EtOAc afforded 2.28 g (83%) of the title compound as a colorless oil. RF: 0.27 (4:1 v/v hexanes/ EtOAc). 1H NMR (300 MHz): δ 1.12-1.23 (m, 2H), 1.51-1.89 (m, 6H), 2.28 (m, 1H), 2.44 (d, J=7.5, 2H), 3.18 (s, 3H), 3.67 (s, 3H). stirred for 3 h The reaction was partitioned between 200 mL of EtOAc and 200 mL 2.0 N HCl After separating the phases the organic layer was washed with 200 mL of 1.0 N NaHCO3 dried over Na2SO4 concentrated

反応条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-(4-Bromophenyl)dioxolane from Example C (7 g, 0.03 mole) was dissolved in 75 mls of THF and cooled to -75° C. under argon. Tert.butyl lithium (29 ml of 1.7M solution in hexane) was added slowly at -76° C. maintaining the temperature such that it never rose above -40° C. After addition was complete, the solution was recooled to -78° C. and 4.2 g, 0.024 moles) of the product of Example B was added in THF. After completion of the addition, the solution was allowed to warm to 0° C., poured into 0.5N KHSO4 and extracted with ethyl acetate. After washing with brine, the extract was dried over Na2SO4. After the solvent was removed, the residue was chromatographed on silica with 10% ethyl acetate/hexane to give 2.8 g of the title compound. maintaining the temperature such that it never rose above -40° C After addition was recooled to -78° C. After completion of the addition to warm to 0° C. extracted with ethyl acetate After washing with brine the extract was dried over Na2SO4 After the solvent was removed the residue was chromatographed on silica with 10% ethyl acetate/hexane

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

実験手順: N,O-Dimethylhydroxylamine hydrochloride (13 g, 0.12mole) was stirred in 250 mls of dichloroethane and cooled to 0° C. under argon. Triethylanime (25 g, 0.25mole) was added dropwise over 15 minutes and the mixture stirred cold for 30 minutes. The acid chloride of Example A (15 g,0.1mole) was dissolved in dichloroethane (50 mls) and added at 0° C. over 1/2 hour to the mixture. The mixture was then stirred for an additional hour at 0° C. The mixture was allowed to warm to room temperature over 2 hours and the solvent was removed in vacuo. The residue was treated with 100 mls of ethyl acetate/ether (25:75) and the triethylamine hydrochloride filtered. The filtrate was stripped of solvent and the residue distilled at 0.1 mm Hg, b.p.=62°-63° C. to give 12 g (70% yield) of the title compound. Triethylanime (25 g, 0.25mole) was added dropwise over 15 minutes added at 0° C. over 1/2 hour to the mixture The mixture was then stirred for an additional hour at 0° C to warm to room temperature over 2 hours the solvent was removed in vacuo The residue was treated with 100 mls of ethyl acetate/ether (25:75) the triethylamine hydrochloride filtered the residue distilled at 0.1 mm Hg, b.p.=62°-63° C.

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

実験手順: A solution of 2.0 mL (15.9 mmol) of cyclopentylacetic acid in 80 mL of CH2Cl2 at 0° C. was treated with 3.7 mL (33.6 mmol) of N-methyl-morpholine and 2.2 mL (16.9 mmol) of isobutyl chloroformate. After stirring for 20 min, 1.61 g (16.5 mmol) of N,O-dimethyl-hydroxylamine.HCl was added. The reaction was warmed to rt and stirred for 3 h. The reaction was partitioned between 200 mL of EtOAc and 200 mL 2.0 N HCl. After separating the phases, the organic layer was washed with 200 mL of 1.0 N NaHCO3, dried over Na2SO4 and concentrated. Flash chromatography on silica gel using 4:1 v/v hexanes/EtOAc afforded 2.28 g (83%) of the title compound as a colorless oil. RF: 0.27 (4:1 v/v hexanes/EtOAc). 1H NMR (300 MHz): δ 1.12-1.23 (m, 2H), 1.51-1.89 (m, 6H), 2.28 (m, 1H), 2.44 (d, J=7.5, 2H), 3.18 (s, 3H), 3.67 (s, 3H). stirred for 3 h The reaction was partitioned between 200 mL of EtOAc and 200 mL 2.0 N HCl After separating the phases the organic layer was washed with 200 mL of 1.0 N NaHCO3 dried over Na2SO4 concentrated

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

実験手順: A solution of 2.0 mL (15.9 mmol) of cyclopentylacetic acid in 80 mL of CH2Cl2 at 0° C. was treated with 3.7 mL (33.6 mmol) of N-methyl-morpholine and 2.2 mL (16.9 mmol) of isobutyl chloroformate. After stirring for 20 min, 1.61 g (16.5 mmol) of N,O-dimethyl-hydroxylamine.HCl was added. The reaction was warmed to rt and stirred for 3 h. The reaction was partitioned between 200 mL of EtOAc and 200 mL 2.0 N HCl. After separating the phases, the organic layer was washed with 200 mL of 1.0 N NaHCO3, dried over Na2SO4 and concentrated. Flash chromatography on silica gel using 4:1 v/v hexanes/EtOAc afforded 2.28 g (83%) of the title compound as a colorless oil. RF: 0.27 (4:1 v/v hexanes/EtOAc). 1H NMR (300 MHz): δ 1.12-1.23 (m, 2H), 1.51-1.89 (m, 6H), 2.28 (m, 1H), 2.44 (d, J=7.5, 2H), 3.18 (s, 3H), 3.67 (s, 3H). stirred for 3 h The reaction was partitioned between 200 mL of EtOAc and 200 mL 2.0 N HCl After separating the phases the organic layer was washed with 200 mL of 1.0 N NaHCO3 dried over Na2SO4 concentrated

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

実験手順: A solution of 2.0 mL (15.9 mmol) of cyclopentylacetic acid in 80 mL of CH2Cl2 at 0° C. was treated with 3.7 mL (33.6 mmol) of N-methyl-morpholine and 2.2 mL (16.9 mmol) of isobutyl chloroformate. After stirring for 20 min, 1.61 g (16.5 mmol) of N,O-dimethyl-hydroxylamine.HCl was added. The reaction was warmed to rt and stirred for 3 h. The reaction was partitioned between 200 mL of EtOAc and 200 mL 2.0 N HCl. After separating the phases, the organic layer was washed with 200 mL of 1.0 N NaHCO3, dried over Na2SO4 and concentrated. Flash chromatography on silica gel using 4:1 v/v hexanes/EtOAc afforded 2.28 g (83%) of the title compound as a colorless oil. RF: 0.27 (4:1 v/v hexanes/ EtOAc). 1H NMR (300 MHz): δ1.12-1.23 (m, 2H), 1.51-1.89 (m, 6H), 2.28 (m, 1H), 2.44 (d, J=7.5, 2H), 3.18 (s, 3H), 3.67 (s, 3H). stirred for 3 h The reaction was partitioned between 200 mL of EtOAc and 200 mL 2.0 N HCl After separating the phases the organic layer was washed with 200 mL of 1.0 N NaHCO3 dried over Na2SO4 concentrated

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

実験手順: A solution of 2.0 mL (15.9 mmol) of cyclopentylacetic acid in 80 mL of CH2Cl2 at 0° C. was treated with 3.7 mL (33.6 mmol) of N-methyl-morpholine and 2.2 mL (16.9 mmol) of isobutyl chloroformate. After stirring for 20 min, 1.61 g (16.5 mmol) of N,O-dimethylhydroxylamine HCl was added. The reaction was warmed to rt and stirred for 3 h. The reaction was partitioned between 200 mL of EtOAc and 200 mL 2.0 N HCl. After separating the phases, the organic layer was washed with 200 mL of 1.0 N NaHCO3, dried over Na2SO4 and concentrated. Flash chromatography on silica gel using 4:1 v/v hexanes/EtOAc afforded 2.28 g (83%) of the title compound: RF: 0.27 (4:1 v/v hexanes/EtOAc). 1H NMR (300 MHz) δ 1.12-1.23 (m, 2H), 1.51-1.89 (m, 6H), 2.28 (m, 1H), 2.44 (d, J=7.5, 2H), 3.18 (s, 3H), 3.67 (s, 3H). stirred for 3 h The reaction was partitioned between 200 mL of EtOAc and 200 mL 2.0 N HCl After separating the phases the organic layer was washed with 200 mL of 1.0 N NaHCO3 dried over Na2SO4 concentrated

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

実験手順: A solution of 2.0 mL (15.9 mmol) of cyclopentylacetic acid in 80 mL of CH2Cl2 at 0° C. was treated with 3.7 mL (33.6 mmol) of N-methyl-morpholine and 2.2 mL (16.9 mmol) of isobutyl chloroformate. After stirring for 20 min, 1.61 g (16.5 mmol) of N,O-dimethyl-hydroxylamine.HCl was added. The reaction was warmed to rt and stirred for 3 h. The reaction was partitioned between 200 mL of EtOAc and 200 mL 2.0 N HCl. After separating the phases, the organic layer was washed with 200 mL of 1.0 N NaHCO3, dried over Na2SO4 and concentrated. Flash chromatography on silica gel using 4:1 v/v hexanes/EtOAc afforded 2.28 g (83%) of the title compound as a colorless oil. RF: 0.27 (4:1 v/v hexanes/ EtOAc). 1H NMR (300 MHz): δ 1.12-1.23 (m, 2H), 1.51-1.89 (m, 6H), 2.28 (m, 1H), 2.44 (d, J=7.5, 2H), 3.18 (s, 3H), 3.67 (s, 3H). stirred for 3 h The reaction was partitioned between 200 mL of EtOAc and 200 mL 2.0 N HCl After separating the phases the organic layer was washed with 200 mL of 1.0 N NaHCO3 dried over Na2SO4 concentrated

反応条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-(4-Bromophenyl)dioxolane from Example C (7 g, 0.03 mole) was dissolved in 75 mls of THF and cooled to -75° C. under argon. Tert.butyl lithium (29 ml of 1.7M solution in hexane) was added slowly at -76° C. maintaining the temperature such that it never rose above -40° C. After addition was complete, the solution was recooled to -78° C. and 4.2 g, 0.024 moles) of the product of Example B was added in THF. After completion of the addition, the solution was allowed to warm to 0° C., poured into 0.5N KHSO4 and extracted with ethyl acetate. After washing with brine, the extract was dried over Na2SO4. After the solvent was removed, the residue was chromatographed on silica with 10% ethyl acetate/hexane to give 2.8 g of the title compound. maintaining the temperature such that it never rose above -40° C After addition was recooled to -78° C. After completion of the addition to warm to 0° C. extracted with ethyl acetate After washing with brine the extract was dried over Na2SO4 After the solvent was removed the residue was chromatographed on silica with 10% ethyl acetate/hexane

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

実験手順: N,O-Dimethylhydroxylamine hydrochloride (13 g, 0.12mole) was stirred in 250 mls of dichloroethane and cooled to 0° C. under argon. Triethylanime (25 g, 0.25mole) was added dropwise over 15 minutes and the mixture stirred cold for 30 minutes. The acid chloride of Example A (15 g,0.1mole) was dissolved in dichloroethane (50 mls) and added at 0° C. over 1/2 hour to the mixture. The mixture was then stirred for an additional hour at 0° C. The mixture was allowed to warm to room temperature over 2 hours and the solvent was removed in vacuo. The residue was treated with 100 mls of ethyl acetate/ether (25:75) and the triethylamine hydrochloride filtered. The filtrate was stripped of solvent and the residue distilled at 0.1 mm Hg, b.p.=62°-63° C. to give 12 g (70% yield) of the title compound. Triethylanime (25 g, 0.25mole) was added dropwise over 15 minutes added at 0° C. over 1/2 hour to the mixture The mixture was then stirred for an additional hour at 0° C to warm to room temperature over 2 hours the solvent was removed in vacuo The residue was treated with 100 mls of ethyl acetate/ether (25:75) the triethylamine hydrochloride filtered the residue distilled at 0.1 mm Hg, b.p.=62°-63° C.