反应详情

Di-tert-butylazodicarboxylate (9.22 g) in methylene chloride (20 ml) was added slowly to a stirred suspension of 4-chloro-6-hydroxy-7-methoxyquinazoline (5.63 g), 4-hydroxy-1-tert-butoxycarbonylpiperidine (8.06 g) and triphenylphosphine (10.5 g) in methylene chloride (100 ml) at 5° C. under an atmosphere of nitrogen. The reaction mixture was allowed to warm to room temperature for 16 hours. The reaction mixture was then evaporated under vacuum and adsorbed onto silica and the product was eluted with isohexane/ethyl acetate/triethylamine (75/24/1 followed by 70/29/1). The fractions containing the desired product were combined and evaporated under vacuum to give tert-butyl 4-[(4-chloro-7-methoxyquinazolin-6-yl)oxy]piperidine-1-carboxylate as a white solid (10.3 g); 1H NMR Spectrum: (DMSO d6) 1.40 (s, 9H), 1.56–1.69 (m, 2H), 1.93–2.04 (m, 2H), 3.20–3.31 (m, 2H), 3.60–3.70 (m, 2H), 4.00 (s, 3H), 4.89 (m, 1H), 7.45 (s, 1H), 7.50 (s, 1H), 8.86 (s, 1H); Mass Spectrum: (M+H)30 394.

1. customThe reaction mixture was then evaporated under vacuum
2. washthe product was eluted with isohexane/ethyl acetate/triethylamine (75/24/1 followed by 70/29/1)
3. additionThe fractions containing the desired product
4. customevaporated under vacuum