tert-butyl N-[(4-fluorophenyl)methylamino]carbamate

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of tert-butyl 2-(4-fluorobenzyl)hydrazinecarboxylate (0.6 g, 2.50 mmol, 1.0 equiv) in EtOH (2.5 mL) was added ethyl formate (0.81 mL, 9.99 mmol, 4.0 equiv) and the reaction mixture heated to 50° C. (oil bath). After stirring 4 h, the reaction was cooled to ambient temperature and stirred 3 d. The reaction was then heated to 50° C. (oil bath) for 3 h at which time more ethyl formate (1.0 mL, 12.28 mmol, 4.9 equiv) was added. After stirring a further 4 h, the reaction was concentrated in vacuo. The crude product was purified by silica gel chromatography (elute with 10-70% ethyl acetate/hexane) to provide the title compound (0.11 g, 16% yield) as a colorless oil which slowly crystallized. Unreacted tert-butyl 2-(4-fluorobenzyl)hydrazinecarboxylate was recovered from the mother liquor. 1H NMR (400 MHz, CDCl3) δ ppm 8.20 (s, 1H), 7.20-7.25 (m, 2H), 7.00-7.08 (m, 2H), 6.27 (s, 1H), 4.58 (s, 2H), 1.43 (s, 9H); LCMS (ES+, (M+H)+) m/z 269.22. the reaction was cooled to ambient temperature stirred 3 d was added After stirring a further 4 h the reaction was concentrated in vacuo The crude product was purified by silica gel chromatography (elute with 10-70% ethyl acetate/hexane)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a cold (0° C.) solution of tert-butyl 2-(4-fluorobenzyl)hydrazinecarboxylate (7.30 g, 30.37 mmol; see Fassler et al., J. Med Chem. 1996, 3203) and diisopropylethylamine (10.70 g, 82.82 mmol) in dichloromethane (200 mL), a solution of 8-(benzyloxy)-2-methyl-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-7-carbonyl chloride (8.80 g, 27.61 mmol; derived from treatment of the corresponding acid with oxalyl chloride in dichloromethane in the presence of catalytic amount of DMF at room temperature) in dichloromethane was added. The resultant mixture was stirred at room temperature overnight. The resultant mixture was washed with aqueous ammonium chloride, and brine. The organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to provide the titled amide. This was used with no further purification. was added The resultant mixture was washed with aqueous ammonium chloride, and brine The organic extract was dried over anhydrous sodium sulfate filtered concentrated under vacuum

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of tert-butyl 2-(4-fluorobenzyl)hydrazinecarboxylate (0.6 g, 2.50 mmol, 1.0 equiv) in EtOH (2.5 mL) was added ethyl formate (0.81 mL, 9.99 mmol, 4.0 equiv) and the reaction mixture heated to 50° C. (oil bath). After stirring 4 h, the reaction was cooled to ambient temperature and stirred 3 d. The reaction was then heated to 50° C. (oil bath) for 3 h at which time more ethyl formate (1.0 mL, 12.28 mmol, 4.9 equiv) was added. After stirring a further 4 h, the reaction was concentrated in vacuo. The crude product was purified by silica gel chromatography (elute with 10-70% ethyl acetate/hexane) to provide the title compound (0.11 g, 16% yield) as a colorless oil which slowly crystallized. Unreacted tert-butyl 2-(4-fluorobenzyl)hydrazinecarboxylate was recovered from the mother liquor. 1H NMR (400 MHz, CDCl3) δ ppm 8.20 (s, 1H), 7.20-7.25 (m, 2H), 7.00-7.08 (m, 2H), 6.27 (s, 1H), 4.58 (s, 2H), 1.43 (s, 9H); LCMS (ES+, (M+H)+) m/z 269.22. the reaction was cooled to ambient temperature stirred 3 d was added After stirring a further 4 h the reaction was concentrated in vacuo The crude product was purified by silica gel chromatography (elute with 10-70% ethyl acetate/hexane)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a cold (0° C.) solution of tert-butyl 2-(4-fluorobenzyl)hydrazinecarboxylate (7.30 g, 30.37 mmol; see Fassler et al., J. Med Chem. 1996, 3203) and diisopropylethylamine (10.70 g, 82.82 mmol) in dichloromethane (200 mL), a solution of 8-(benzyloxy)-2-methyl-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-7-carbonyl chloride (8.80 g, 27.61 mmol; derived from treatment of the corresponding acid with oxalyl chloride in dichloromethane in the presence of catalytic amount of DMF at room temperature) in dichloromethane was added. The resultant mixture was stirred at room temperature overnight. The resultant mixture was washed with aqueous ammonium chloride, and brine. The organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to provide the titled amide. This was used with no further purification. was added The resultant mixture was washed with aqueous ammonium chloride, and brine The organic extract was dried over anhydrous sodium sulfate filtered concentrated under vacuum

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of tert-butyl 2-(4-fluorobenzyl)hydrazinecarboxylate (0.6 g, 2.50 mmol, 1.0 equiv) in EtOH (2.5 mL) was added ethyl formate (0.81 mL, 9.99 mmol, 4.0 equiv) and the reaction mixture heated to 50° C. (oil bath). After stirring 4 h, the reaction was cooled to ambient temperature and stirred 3 d. The reaction was then heated to 50° C. (oil bath) for 3 h at which time more ethyl formate (1.0 mL, 12.28 mmol, 4.9 equiv) was added. After stirring a further 4 h, the reaction was concentrated in vacuo. The crude product was purified by silica gel chromatography (elute with 10-70% ethyl acetate/hexane) to provide the title compound (0.11 g, 16% yield) as a colorless oil which slowly crystallized. Unreacted tert-butyl 2-(4-fluorobenzyl)hydrazinecarboxylate was recovered from the mother liquor. 1H NMR (400 MHz, CDCl3) δ ppm 8.20 (s, 1H), 7.20-7.25 (m, 2H), 7.00-7.08 (m, 2H), 6.27 (s, 1H), 4.58 (s, 2H), 1.43 (s, 9H); LCMS (ES+, (M+H)+) m/z 269.22. the reaction was cooled to ambient temperature stirred 3 d was added After stirring a further 4 h the reaction was concentrated in vacuo The crude product was purified by silica gel chromatography (elute with 10-70% ethyl acetate/hexane)