Ammonium Chloride → (2R,4R)-2-[(4S,5S)-3-Acetyl-4-(3,5-difluoro-benzyl)-2,2-dimethyl-oxazolidin-5-yl]-4-hydroxy-4-trifluoromethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 732597Notes

Reaction equation

HRID 732597 reaction equation
[F:1][C:2]([Si](C)(C)C)([F:4])[F:3].[C:9]([O:13][C:14]([N:16]1[CH2:20][C:19](=[O:21])[CH2:18][C@@H:17]1[C@H:22]1[O:26][C:25]([CH3:28])([CH3:27])[N:24]([C:29](=[O:31])[CH3:30])[C@H:23]1[CH2:32][C:33]1[CH:38]=[C:37]([F:39])[CH:36]=[C:35]([F:40])[CH:34]=1)=[O:15])([CH3:12])([CH3:11])[CH3:10].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C.O>[C:9]([O:13][C:14]([N:16]1[CH2:20][C@@:19]([OH:21])([C:2]([F:4])([F:3])[F:1])[CH2:18][C@@H:17]1[C@H:22]1[O:26][C:25]([CH3:27])([CH3:28])[N:24]([C:29](=[O:31])[CH3:30])[C@H:23]1[CH2:32][C:33]1[CH:34]=[C:35]([F:40])[CH:36]=[C:37]([F:39])[CH:38]=1)=[O:15])([CH3:10])([CH3:11])[CH3:12]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium Fluoride2×HCID 68814480(R)-2-[(4S,5S)-3-Acetyl-4-(3,5-difluoro-benzyl)-2,2-dimethyl-oxazolidin-5-yl]-4-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68814597(2R,4R)-2-[(4S,5S)-3-Acetyl-4-(3,5-difluoro-benzyl)-2,2-dimethyl-oxazolidin-5-yl]-4-hydroxy-4-trifluoromethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Add (trifluoromethyl)trimethylsilane (0.28 mL, 1.88 mmol) to an ice cold solution of (R)-2-[(4S,5S)-3-acetyl-4-(3,5-difluoro-benzyl)-2,2-dimethyl-oxazolidin-5-yl]-4-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (0.50 g, 1.11 mmol) in tetrahydrofuran (10 mL). Add tetrabutylammonium fluoride (0.035 mL of 1M solution in tetrahydrofuran). Stir 2.5 hours and add tetrabutylammonium fluoride (2 mL of 1M solution in tetrahydrofuran) and stir 2 hours. Add saturated aqueous ammonium chloride (3 mL) and dilute with ethyl acetate and water. Wash organic layer with saturated aqueous sodium chloride, dry with magnesium sulfate and purify on silica gel with dichloromethane/ethyl acetate mixtures to give the desired compound and 10% hydroxy diastereomer as a foam (0.48 g, 83%).

Workup

  1. stirringstir 2 hours
  2. dry with materialWash organic layer with saturated aqueous sodium chloride, dry with magnesium sulfate
  3. custompurify on silica gel with dichloromethane/ethyl acetate

Sources & evidence

ORD record
ord-0054401ffa7442ccb201d4ad5c3c4ff4
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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