tert-butyl N-[(8S)-6-azaspiro[3.4]octan-8-yl]carbamate

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

実験手順: Benzyl chloroformate (0.224 mL, 1.569 mmol) was added dropwise to a stirred solution of (S)-tert-butyl 6-azaspiro[3.4]octan-8-ylcarbamate (0.2368 g, 1.046 mmol) in dichloromethane (7 mL) and a solution of sodium carbonate (69.1 mg, 0.652 mmol) in Water (1.05 mL) @ 0° C. Stirring of the biphasic reaction was continued @ 0° C. for 45 minutes. +/−MS analysis after 16 hrs indicated that essentially no starting material remained (m/e 361.3, M+H for desired product). A small amount of water was added and the layers were separated. The CH2Cl2 layer was washed with brine, dried over Na2SO4, and concentrated under vacuum to yield 0.433 g of the desired product as a viscous yellow oil. Flash chromatography on silica gel (Teledyne-Isco RediSep Rf 12 g column), eluting with 100 mL ea of 95:5, 90:10, and 200 mL of 80:20 hexane:EtOAc yielded 0.324 g of the title compound as a viscous colorless oil that slowly solidifies upon standing under vacuum to a white solid. +/−MS: m/e 361.3 (M+H), 305.2 (M+H-56 isobutylene), 261.2 (M+H-Boc). 1H NMR (400 MHz, CHLOROFORM-d) δ 7.45-7.32 (m, 5H), 5.15 (s, 2H), 4.53 (br. s., 1H), 4.14-4.01 (m, 1H), 3.70-3.50 (m, 2H), 3.47-3.24 (m, 2H), 2.19-2.09 (m, 1H), 2.05-1.83 (m, 5H), 1.49 (s, 9H). +/−MS analysis after 16 hrs indicated

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

実験手順: A stirred solution of (S)-tert-butyl (6-benzyl-6-azaspiro[3.4]octan-8-yl)carbamate (enantiopure Intermediate 13, 0.364 g, 1.149 mmol) in Ethanol (21.3 mL) with Pd/C (10% b/w) (0.291 g, 2.73 mmol), was charged with hydrogen gas @ 50 psi in a pressure bottle and agitated for 4 hrs. +/−MS analysis after 3 hrs 15 min indicated that essentially no starting material remained (m/e 227.2, M+H for desired product). The catalyst was removed by filtration, and the filtrate was concentrated under vacuum to yield 0.247 g of the desired product as a tan oil. +/−MS: m/e 227.2 (M+H). 1H NMR (400 MHz, CHLOROFORM-d) δ 4.66 (br. s., 1H), 3.96 (br. s., 1H), 3.24 (dd, J=11.3, 6.1 Hz, 1H), 3.05 (d, J=11.0 Hz, 1H), 2.89 (d, J=11.2 Hz, 1H), 2.72 (dd, J=11.6, 3.4 Hz, 1H), 2.13 (dd, J=9.6, 3.4 Hz, 3H), 2.04-1.71 (m, 5H), 1.46 (s, 9H). +/−MS analysis after 3 hrs 15 min indicated

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

実験手順: A stirred solution of (S)-tert-butyl (6-benzyl-6-azaspiro[3.4]octan-8-yl)carbamate (enantiopure Intermediate 13, 0.364 g, 1.149 mmol) in Ethanol (21.3 mL) with Pd/C (10% b/w) (0.291 g, 2.73 mmol), was charged with hydrogen gas @ 50 psi in a pressure bottle and agitated for 4 hrs. +/−MS analysis after 3 hrs 15 min indicated that essentially no starting material remained (m/e 227.2, M+H for desired product). The catalyst was removed by filtration, and the filtrate was concentrated under vacuum to yield 0.247 g of the desired product as a tan oil. +/−MS: m/e 227.2 (M+H). 1H NMR (400 MHz, CHLOROFORM-d) δ 4.66 (br. s., 1H), 3.96 (br. s., 1H), 3.24 (dd, J=11.3, 6.1 Hz, 1H), 3.05 (d, J=11.0 Hz, 1H), 2.89 (d, J=11.2 Hz, 1H), 2.72 (dd, J=11.6, 3.4 Hz, 1H), 2.13 (dd, J=9.6, 3.4 Hz, 3H), 2.04-1.71 (m, 5H), 1.46 (s, 9H). +/−MS analysis after 3 hrs 15 min indicated

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

実験手順: Benzyl chloroformate (0.224 mL, 1.569 mmol) was added dropwise to a stirred solution of (S)-tert-butyl 6-azaspiro[3.4]octan-8-ylcarbamate (0.2368 g, 1.046 mmol) in dichloromethane (7 mL) and a solution of sodium carbonate (69.1 mg, 0.652 mmol) in Water (1.05 mL) @ 0° C. Stirring of the biphasic reaction was continued @ 0° C. for 45 minutes. +/−MS analysis after 16 hrs indicated that essentially no starting material remained (m/e 361.3, M+H for desired product). A small amount of water was added and the layers were separated. The CH2Cl2 layer was washed with brine, dried over Na2SO4, and concentrated under vacuum to yield 0.433 g of the desired product as a viscous yellow oil. Flash chromatography on silica gel (Teledyne-Isco RediSep Rf 12 g column), eluting with 100 mL ea of 95:5, 90:10, and 200 mL of 80:20 hexane:EtOAc yielded 0.324 g of the title compound as a viscous colorless oil that slowly solidifies upon standing under vacuum to a white solid. +/−MS: m/e 361.3 (M+H), 305.2 (M+H-56 isobutylene), 261.2 (M+H-Boc). 1H NMR (400 MHz, CHLOROFORM-d) δ 7.45-7.32 (m, 5H), 5.15 (s, 2H), 4.53 (br. s., 1H), 4.14-4.01 (m, 1H), 3.70-3.50 (m, 2H), 3.47-3.24 (m, 2H), 2.19-2.09 (m, 1H), 2.05-1.83 (m, 5H), 1.49 (s, 9H). +/−MS analysis after 16 hrs indicated

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

実験手順: A stirred solution of (S)-tert-butyl (6-benzyl-6-azaspiro[3.4]octan-8-yl)carbamate (enantiopure Intermediate 13, 0.364 g, 1.149 mmol) in Ethanol (21.3 mL) with Pd/C (10% b/w) (0.291 g, 2.73 mmol), was charged with hydrogen gas @ 50 psi in a pressure bottle and agitated for 4 hrs. +/−MS analysis after 3 hrs 15 min indicated that essentially no starting material remained (m/e 227.2, M+H for desired product). The catalyst was removed by filtration, and the filtrate was concentrated under vacuum to yield 0.247 g of the desired product as a tan oil. +/−MS: m/e 227.2 (M+H). 1H NMR (400 MHz, CHLOROFORM-d) δ 4.66 (br. s., 1H), 3.96 (br. s., 1H), 3.24 (dd, J=11.3, 6.1 Hz, 1H), 3.05 (d, J=11.0 Hz, 1H), 2.89 (d, J=11.2 Hz, 1H), 2.72 (dd, J=11.6, 3.4 Hz, 1H), 2.13 (dd, J=9.6, 3.4 Hz, 3H), 2.04-1.71 (m, 5H), 1.46 (s, 9H). +/−MS analysis after 3 hrs 15 min indicated