Triphenylphosphine → HCID 58318673, compound

Participants

Reaction Steps

A solution of DEAD (0.329 ml, 2.08 mmol) in DCM (2 ml) was added to as stirred suspension of 4-chloro-7-methoxyquinazolin-6-ol (283 mg, 1.74 mmol prepared as described in Example 16 of WO03/082831),1-tert-butyl 2-methyl (2S,4S)-4-hydroxypiperidine-1,2-dicarboxylate (11) (450 mg, 2.08 mmol) and triphenylphosphine (547 mg, 2.098 mmol) in DCM (10 ml), such that the internal temperature remained <30° C. The reaction mixture was stirred overnight and evaporated to dryness. The residues were purified by column chromatography on SiO2 eluting with increasingly polar mixtures of DCM/methanol (100/0-95/5). The fractions containing the desired product were combined and evaporated to give 1-tert-butyl 2-methyl (2S,4R)-4-[(4-chloro-7-methoxyquinazolin-6-yl)oxy]piperidine-1,2-dicarboxylate (12) as a gum (478 mg, 79%): 1H NMR Spectrum: (DMSO-d6) δ1.39-1.46 (10H, m), 1.73-1.84 (1H, m), 1.92-2.03 (1H, m), 2.10-2.18 (1H, m), 2.60-2.69 (1H, m), 3.15-3.40 (3H, m), 3.74-3.85 (1H, m), 4.01 (3H, s), 4.61-4.73 (1H, m), 5.06 (1H, s), 7.43 (1H, s), 7.47 (1H, s), 8.89 (1H, s), 8.97 (1H, s); Mass Spectrum: (M+H)+ 452.

Provenance & Evidence