Triphenylphosphine → tert-butyl(2R)-2-{[(7-(benzyloxy)-3-{[(2,2-dimethylpropanoyl)oxy]methyl}-4-oxo-3,4-dihydroquinazolin-5-yl)oxy]methyl}pyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

tert-butyl (2R)-2-(hydroxymethyl)pyrrolidine-1-carboxylate (1.70 g, 8.6 mmol) was added to a solution of [7-(benzyloxy)-5-hydroxy-4-oxoquinazolin-3(4H)-yl]methyl pivalate (see WO01/094341, 3.0 g, 7.8 mmol) and PS-triphenylphosphine (1.5 mmol/g, 7.2 g, 4.2 mmol) in dichloromethane (120 ml). The reaction mixture was cooled to 0° C. and then a solution of di-tert-butylazodicarboxylate (2.1 g, 9.3 mmol) in dichloromethane (15 ml) was added dropwise over 30 minutes. The mixture was allowed to warn to room temperature and then stirred for 2 hours. The mixture was evaporated under reduced pressure and the residue was purified by silica gel chromatography eluting with a 0 to 10% mixture methanol in dichloromethane to give tert-butyl (2R)-2-{[(7-(benzyloxy)-3-{[(2,2-dimethylpropanoyl)oxy]methyl}-4-oxo-3,4-dihydroquinazolin-5-yl)oxy]methyl}pyrrolidine-1-carboxylate (1.58 g, 36% yield):

Provenance & Evidence