2-Bromobenzoyl chloride → (cis)-1-o-bromobenzoyl-4-hydroxy-L-proline methyl ester

Participants

Reaction Steps

Into a flame-dried 100 ml three-necked round-bottomed flask containing 30 ml of distilled THF was placed 3.00 g (16.575 mmol) of (cis)-4-hydroxy-L-proline, methyl ester; the vessel was immersed in an ice/water bath and the suspension was allowed to stir under argon for 5 minutes. At this time, 6.35 ml (36.465 mmol) of diisopropylethylamine was added slowly via syringe; the mixture was allowed to stir for 10 minutes, whereupon 3.64 g (16.576 mmol) of 2-bromobenzoyl chloride was added dropwise via syringe over the course of 10 minutes. The mixture was allowed to stir at 0° for 2 hours then gradually brought to room temperature overnight. The mixture was concentrated under vacuum to a minimal volume, transferred to a separatory funnel, and diluted with 100 ml of ethyl acetate, then washed with 1N HCl (2×30 ml), saturated sodium bicarbonate (2×30 ml), and brine (30 ml). The organic solution was dried over sodium sulfate, filtered, and concentrated under vacuum. Recrystallization from hot ethyl acetate yielded 3.034 g (55.6%) of the title compound, m.p. 145.5°-146.8° C.; a second recrystallization of the mother liquor yielded 1.726 g to bring the net yield to 4.760 g (87.3%).

Provenance & Evidence