Trifluoroacetic acid → (3RS,4SR)-1-Benzyl-4-(3,4-difluoro-phenyl)-pyrrolidine-3-carboxylic acid

HRID 906939Notes

Reaction equation

HRID 906939 reaction equation
CO[CH2:3][N:4]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:5][Si](C)(C)C.[F:17][C:18]1[CH:19]=[C:20](/[CH:25]=[CH:26]/[C:27]([OH:29])=[O:28])[CH:21]=[CH:22][C:23]=1[F:24].FC(F)(F)C(O)=O>C1COCC1>[CH2:10]([N:4]1[CH2:3][CH:25]([C:20]2[CH:21]=[CH:22][C:23]([F:24])=[C:18]([F:17])[CH:19]=2)[CH:26]([C:27]([OH:29])=[O:28])[CH2:5]1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 2733300trans-3,4-Difluorocinnamic acid

Product 1

HCID 67131486(3RS,4SR)-1-Benzyl-4-(3,4-difluoro-phenyl)-pyrrolidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-(methoxymethyl)-N-(phenylmethyl)-N-(trimethylsilyl)methylamine (48.3 g, 204 mmol) and (E)-3-(3,4-difluoro-phenyl)-acrylic acid (15 g, 81.5 mmol) in THF (200 mL) was added trifluoroacetic acid (0.312 mL, 0.0041 mol) at 0° C. The mixture was gradually warmed to room temperature and stirred overnight. It was then concentrated in vaccuo and the residue was diluted with n-heptane (500 mL) followed by vigorous stirring for 1 hour. The resulted white precipitation was collected and washed with heptane affording 26 g (100%) of the title compound as a white solid. MS m/e: 318.1 (M+H+).

Workup

  1. concentrationIt was then concentrated in vaccuo
  2. additionthe residue was diluted with n-heptane (500 mL)
  3. stirringby vigorous stirring for 1 hour
  4. customThe resulted white precipitation
  5. customwas collected
  6. washwashed with heptane affording 26 g (100%) of the title compound as a white solid

Sources & evidence

ORD record
ord-985235d364e248e0bd56d1940297826a
Source dataset
uspto-grants-2011_09
Patent number
US08012998B2

Reaction notes

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