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

HRID 906931Notes

Reaction equation

HRID 906931 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl: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]([Cl:19])=[C:15]([Cl: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 16244042(3RS,4SR)-1-Benzyl-4-(3,4-dichloro-phenyl)-pyrrolidine-3-carboxylic acid

Product 1

HCID 67131796(S)-4-benzyl-3-[(3R,4S)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidine-3-carbonyl]-oxazolidin-2-oneYield 49%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3RS,4SR)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidine-3-carboxylic acid (described herein above) (13.39 g, 0.038 mol) in THF (200 mL) at −20° C. were added triethylamine (13.32 mL, 0.096 mol) and pivaloyl chloride (11.76 mL, 0.096 mol) subsequently. Stirring was continued for two hours at the same temperature, and to this mixture were added (S)-4-benzyl-oxazolidin-2-one (8.13 g, 0.046 mol) and lithium chloride (1.94 g, 0.046 mol). 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, 1:2) to yield (S)-4-benzyl-3-[(3R,4S)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidine-3-carbonyl]-oxazolidin-2-one 9.47 g (49%) as a white solid ES-MS m/e: 509.3 (M+H+) and (S)-4-benzyl-3-[(3S,4R)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidine-3-carbonyl]-oxazolidin-2-one 9.40 g (48%) as a white solid ES-MS m/e: 509.3 (M+H+).

Workup

  1. customat −20° C.
  2. stirringstirred overnight
  3. washwashed with water two times and saturated sodiumbicarbonate
  4. customThe separated organic phase was dried on Na2SO4
  5. concentrationconcentrated under vacuo
  6. customThe two diastereoisomeres were separated by column chromatography (SiO2, EtOAc/H, 1:2)

Sources & evidence

ORD record
ord-07c76eed884844a1987629d4ffec85db
Source dataset
uspto-grants-2011_09
Patent number
US08012998B2

Reaction notes

Loading…