反应详情

Di-tert-butylazodicarboxylate (1.64 g, 7.14 mmol) in methylene chloride (20 ml) was added slowly to a stirred suspension of 4-Chloro-6-methoxyquinazolin-7-ol (1.0 g, 4.76 mmol, prepared as described in WO2004041829, Example 1 therein (preparation of starting materials)), 4-hydroxy-1-tert-butoxycarbonylpiperidine (1.44 g, 7.14 mmol) and triphenylphosphine (1.87 g, 7.14 mmol) in methylene chloride (50 ml) at 5° C. under an atmosphere of nitrogen. The reaction mixture was allowed to warm to room temperature for 18 hours. The reaction mixture was then filtered and purified by flash chromatography on silica eluting with increasingly polar mixtures of isohexane/ethyl acetate/triethylamine (75/24/1 followed by 0/99/1). The fractions containing the desired product were combined and evaporated under vacuum to give tert-butyl 4-[(4-chloro-6-methoxyquinazolin-7-yl)oxy]piperidine-1-carboxylate as a white solid (1.75 g, 93.4%); 1H NMR Spectrum: (DMSO d6) 1.40 (s, 9H), 1.5-1.7 (m, 2H), 1.9-2.1 (m, 2H), 3.1-3.3 (m, 2H), 3.60-3.80 (m, 2H), 3.95 (s, 3H), 4.92 (m, 1H), 7.38 (s, 1H), 7.58 (s, 1H), 8.83 (s, 1H); Mass Spectrum: (M+H)+ 394.

1. customprepared
2. filtrationThe reaction mixture was then filtered
3. custompurified by flash chromatography on silica eluting
4. temperaturewith increasingly polar mixtures of isohexane/ethyl acetate/triethylamine (75/24/1 followed by 0/99/1)
5. additionThe fractions containing the desired product
6. customevaporated under vacuum