Triethylamine → (S)-4-benzyl-3-[(3R,4S)-1-benzyl-4-(3,4-difluoro-phenyl)-pyrrolidine-3-carbonyl]-oxazolidin-2-one

HRID 906940Notes

Reaction equation

HRID 906940 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=2)[CH:10]([C:21](O)=[O:22])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.[CH2:38]([C@H:45]1[CH2:49][O:48][C:47](=[O:50])[NH:46]1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.[Cl-].[Li+]>C1COCC1.C(OCC)(=O)C>[CH2:38]([C@H:45]1[CH2:49][O:48][C:47](=[O:50])[N:46]1[C:21]([C@@H:10]1[C@@H:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=2)[CH2:12][N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:9]1)=[O:22])[C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 433294Lithium ChlorideHCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 67131486(3RS,4SR)-1-Benzyl-4-(3,4-difluoro-phenyl)-pyrrolidine-3-carboxylic acid

Product 1

HCID 67131567(S)-4-benzyl-3-[(3R,4S)-1-benzyl-4-(3,4-difluoro-phenyl)-pyrrolidine-3-carbonyl]-oxazolidin-2-oneYield 48%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3RS,4SR)-1-benzyl-4-(3,4-difluoro-phenyl)-pyrrolidine-3-carboxylic acid (25 g, 78.8 mmol) in THF (350 mL) at -20° C. were added triethylamine (27.45 mL, 197 mmol) and pivaloyl chloride (24.2 mL, 197 mmol) subsequently. Stirring was continued for two hours at the same temperature, and to this mixture were added (S)-4-Benzyl-oxazolidin-2-one (14.7 g, 82.7 mmol) and lithium chloride (3.67 g, 86.7 mmol). The reaction mixture was gradually warmed to room temperature and stirred overnight. The reaction mixture was diluted with ethyl acetate and washed with water two times and saturated sodiumbicarbonate. The separated organic phase was dried on Na2SO4 and concentrated under vacuo. The two diastereoisomeres were separated by column chromatography (SiO2, EtOAc/H, 15:85) to yield (S)-4-benzyl-3-[(3R,4S)-1-benzyl-4-(3,4-difluoro-phenyl)-pyrrolidine-3-carbonyl]-oxazolidin-2-one 18 g (48%) as awhite solid. MS m/e: 477.1 (M+H+).

Workup

  1. stirringstirred overnight
  2. washwashed with water two times and saturated sodiumbicarbonate
  3. customThe separated organic phase was dried on Na2SO4
  4. concentrationconcentrated under vacuo
  5. customThe two diastereoisomeres were separated by column chromatography (SiO2, EtOAc/H, 15:85)

Sources & evidence

ORD record
ord-f818292fbe1e41d8a156ba3a6ed4ed08
Source dataset
uspto-grants-2011_09
Patent number
US08012998B2

Reaction notes

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