Sodium Chloride → 4-[(1R,2S)-3-(3,5-Difluorophenyl)-1-hydroxy-2-nitropropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

HRID 20332

Reaction equation

HRID 20332 reaction equation
[CH:1]([C@H:3]1[CH2:7][O:6][C:5]([CH3:9])([CH3:8])[N:4]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[O:2].[F:17][C:18]1[CH:23]=[C:22]([CH2:24][CH2:25][N+:26]([O-:28])=[O:27])[CH:21]=[C:20]([F:29])[CH:19]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[Na+]>O1CCCC1.C(OCC)(=O)C.O>[C:13]([O:12][C:10]([N:4]1[CH:3]([C@@H:1]([OH:2])[C@@H:25]([N+:26]([O-:28])=[O:27])[CH2:24][C:22]2[CH:23]=[C:18]([F:17])[CH:19]=[C:20]([F:29])[CH:21]=2)[CH2:7][O:6][C:5]1([CH3:9])[CH3:8])=[O:11])([CH3:16])([CH3:15])[CH3:14]

Participants

8

Reactant 4

HCID 5234Sodium ChlorideHCID 1787923-Boc-2,2-dimethyloxazolidine-4-carboxaldehyde, (R)-(+)-HCID 2724141Tetrabutylammonium FluorideHCID 552507531,3-Difluoro-5-(2-nitroethyl)benzene

Product 1

HCID 685640904-[(1R,2S)-3-(3,5-Difluorophenyl)-1-hydroxy-2-nitropropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl esterYield 43.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Dissolve (R)-tert-butyl 4-formyl-2,2-dimethyloxazolidine-3-carboxylate (1.60 g, 6.98 mmol) and 1,3-difluoro-5-(2-nitroethyl)-benzene (1.40 g, 7.48 mmol) in dry tetrahydrofuran (14 mL) and add 1 M tetrabutylammonium fluoride (TBAF) in tetrahydrofuran (7.0 ml, 7.0 mmol) in one portion. Stir the resulting mixture for 30 minutes and then dilute with ethyl acetate. Quickly shake the mixture with water and then add a small amount of saturated aqueous sodium chloride. Discard the aqueous phase and wash the organic phase again with water (twice) followed by saturated aqueous sodium chloride. Dry the organic solution over magnesium sulfate (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 0:100 to 20:80 ethyl acetate:hexanes) to give the coupling product as an approximately ˜80:20 mixture of diastereomers (2.45 g, 84%). Isolate the major isomer by recrystallization of the diastereomeric mixture from dichloromethane (dichloromethane)/hexanes or diethyl ether/hexanes) to give 1.26 g of the desired compound as a white crystalline solid.

Workup

  1. washwash the organic phase again with water (twice)
  2. dry with materialDry the organic solution over magnesium sulfate (magnesium sulfate)
  3. filtrationfilter
  4. concentrationconcentrate
  5. custompurify
  6. wash(silica gel chromatography, eluting with 0:100 to 20:80 ethyl acetate:hexanes)
  7. customto give the coupling product
  8. additionas an approximately ˜80:20 mixture of diastereomers (2.45 g, 84%)
  9. customIsolate the major isomer
  10. customby recrystallization of the diastereomeric mixture from dichloromethane (dichloromethane)/hexanes or diethyl ether/hexanes)

Sources & evidence

ORD record
ord-1f44a773f3ad4bc9a016ab8011ad7cc1
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Linked notes

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