Citric Acid → (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl fluoride

Participants

Reaction Steps

2,4,6-Trifluoro-1,3,5-triazine (10.7 g, 79 mmol) was added into a solution of pyridine (6.4 ml, 79 mmol) and (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (WO 2009061879) (22 g, 72.0 mmol) in dichloromethane (348 ml) at room temperature. The resulting solution was stirred overnight. Dichloromethane (300 mL) was added to the reaction solution, followed by 1000 mL of 5% citric acid, and the mixture was filtrated. The solids were washed with DCM (300 ml). The organic layer of the filtrate was separated and washed with sat. NaHCO3 (2×300 mL). The organic layer was dried over Na2SO4, filtered and concentrated to yield a yellow oil, which was purified by silica gel chromatography (CombiFlash, Column: 220 g; 0-20% ethyl acetate in hexane; 50 min) to provide (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl fluoride (14.32 g, 64.7% yield) as a colorless oil.

Provenance & Evidence