Lithium hydroxide, monohydrate → (3S,4R)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidine-3-carboxylic acid

HRID 587405Notes

Reaction equation

HRID 587405 reaction equation
C[O:2][C:3]([C@H:5]1[C@H:9]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([F:17])[CH:11]=2)[CH2:8][N:7]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:6]1)=[O:4].O[Li].O>O.CO>[CH2:18]([N:7]1[CH2:8][C@@H:9]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([F:17])[CH:11]=2)[C@H:5]([C:3]([OH:4])=[O:2])[CH2:6]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 58303025(3S,4R)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidine-3-carboxylic acid methyl ester

Product 1

HCID 58303139(3S,4R)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidine-3-carboxylic acidYield 80.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 19.5 g (56 mmol) (3S,4R)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidine-3-carboxylic acid methyl ester and 14.1 g (337 mmol) LiOH.H2O in water (100 mL) and methanol (10 mL) was heated to 80° C. for 45 min. The organic solvents were removed under vacuum and the aqueous phase acidified with 2N HCl tp pH=1-2. The precipitate was filtered off, washed with acetonitrile and dried to yield 15.1 g (73%) of the title compound as off-white solid. MS m/e: 334.1 [M+H]+.

Workup

  1. customThe organic solvents were removed under vacuum
  2. filtrationThe precipitate was filtered off
  3. washwashed with acetonitrile
  4. customdried

Sources & evidence

ORD record
ord-1be98c7d9cbb4354a42e21c85509fae4
Source dataset
uspto-grants-2016_01
Patent number
US09226916B2

Reaction notes

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