반응 #89668

반응 방정식

HCl

racemic methyl (3R,4S)-1-(4-fluorobenzoyl)-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl]-3-[(trifluoroacetyl)amino]pyrrolidine-3-carboxylate

Lithium hydroxide monohydrate

lithium hydroxide monohydrate

→

racemic (3R,4S)-3-amino-4-[3-(dihydroxyboryl)propyl]-1-(4-fluorobenzoyl)pyrrolidine-3-carboxylic acid hydrochloride

수율 30.0%

용매

water

THF

water

반응 조건

후처리

1. 1
   기타the mixture was sparged with nitrogen for 10 min
2. 2
   workup.ADDITIONwas added
3. 3
   세척The resulting solution was washed with ethyl acetate (2×20 mL) and methylene chloride (2×20 mL)
4. 4
   농축The aqueous phase was concentrated under reduced pressure
5. 5
   기타purified by reverse phase HPLC
6. 6
   농축concentrated
7. 7
   workup.DISSOLUTIONre-dissolved in 1M aqueous HCl
8. 8
   농축concentrated

실험 절차

A stirred solution of racemic methyl (3R,4S)-1-(4-fluorobenzoyl)-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl]-3-[(trifluoroacetyl)amino]pyrrolidine-3-carboxylate (200 mg, 0.377 mmol) in THF 94.2 mL) and water (3.7 mL) was sparged with nitrogen for 5 min. Lithium hydroxide monohydrate (33.2 mg, 0.792 mmol) was added, and the mixture was sparged with nitrogen for 10 min and stirred under nitrogen at room temperature for 4 days, during which additional lithium hydroxide monohydrate (39.6 mg, 0.943 mmol) was added. The mixture was diluted with water (5 mL) and acidified to pH<1 with 3 M aqueous HCl. The resulting solution was washed with ethyl acetate (2×20 mL) and methylene chloride (2×20 mL). The aqueous phase was concentrated under reduced pressure and purified by reverse phase HPLC. Product fractions were pooled, concentrated, re-dissolved in 1M aqueous HCl, concentrated and lyophilized to give racemic (3R,4S)-3-amino-4-[3-(dihydroxyboryl)propyl]-1-(4-fluorobenzoyl)pyrrolidine-3-carboxylic acid hydrochloride (42 mg, 30%) as a white amorphous solid. MS (ESI+) m/z 321 (M−H2O+H+), 303 (M−2 H2O+H+) and MS (ESI−) m/z 319 (M−H2O−H+).

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