Triphenylphosphine → tert-Butyl (2R,4R)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-[({4-[3-chloro-4-fluoro-anilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidine-1-carboxylate

Participants

Reaction Steps

Di-tert-butylazodicarboxylate (DTAD, 914 mg) was added in one portion to a mixture of 4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-ol (848 mg), tert-butyl (2R,4R)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-(hydroxymethyl)-pyrrolidine-1-carboxylate (1.10 g), and triphenylphosphine (1.04 g) in DCM (100 ml) at room temperature, under an atmosphere of nitrogen. The reaction mixture was stirred at room temperature for 24 hours and then concentrated in vacuo to leave a brown oil. Purification by column chromatography, using 0-50% ethyl acetate in hexane as eluent, gave tert-butyl (2R,4R)-4-{[tert-butyl(dimethyl)silyl]-oxy}-2-[({4-[3-chloro-4-fluoroanilino]-7-methoxy-quinazolin-5-yl}oxy)methyl]-pyrrolidine-1-carboxylate as a white solid (839 mg, 50%); Mass spectrum MH+ 633.

Provenance & Evidence