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

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%).

1. customthe vessel was immersed in an ice/water bath
2. additionwas added dropwise via syringe over the course of 10 minutes
3. stirringto stir at 0° for 2 hours
4. waitthen gradually brought to room temperature overnight
5. concentrationThe mixture was concentrated under vacuum to a minimal volume
6. customtransferred to a separatory funnel
7. additiondiluted with 100 ml of ethyl acetate
8. washwashed with 1N HCl (2×30 ml), saturated sodium bicarbonate (2×30 ml), and brine (30 ml)
9. dry with materialThe organic solution was dried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated under vacuum
12. customRecrystallization from hot ethyl acetate

ORDレコード

ord-9c2a3c83e3444c3ab2ba00631a1e403a

出典データセット

uspto-grants-1990_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US04912231