Acetonitrile → (2S)-1-[(tert-butoxy)carbonyl]-4,4-difluoropyrrolidine-2-carboxylic acid

HRID 469753

Reaction equation

HRID 469753 reaction equation
O.[OH-].[Li+].C[O:5][C:6]([C@@H:8]1[CH2:12][C:11]([F:14])([F:13])[CH2:10][N:9]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[O:7].C(#N)C>O>[C:18]([O:17][C:15]([N:9]1[CH2:10][C:11]([F:13])([F:14])[CH2:12][C@H:8]1[C:6]([OH:7])=[O:5])=[O:16])([CH3:21])([CH3:19])[CH3:20]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 168937Lithium hydroxide, monohydrateHCID 11129200N-Boc-4,4-difluoro-L-proline methyl ester

Product 1

HCID 22977458(2S)-1-[(tert-butoxy)carbonyl]-4,4-difluoropyrrolidine-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Lithium hydroxide monohydrate (469 mg, 11.2 mmol) is added to a solution of (S)-4,4-difluoro-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (1.48 g, 5.59 mmol) in 3:1 acetonitrile in water (20 mL). The reaction is stirred at room temperature for 2 hours. The reaction mixture is concentrated under reduced pressure and diluted with water and extracted with ether. The aqueous layer is acidified to PH˜1 and extracted with ethyl acetate 3 times. The organics are combined and washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to yield the title compound. ESI m/z 152 [M+H+−100].

Workup

  1. concentrationThe reaction mixture is concentrated under reduced pressure
  2. additiondiluted with water
  3. extractionextracted with ether
  4. extractionextracted with ethyl acetate 3 times
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-59361dd4390d44778a953c0f3f7efcb7
Source dataset
uspto-grants-2014_01
Patent number
US08629157B2

Linked notes

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