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

HRID 20332

반응식

HRID 20332 반응식
[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]

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-1f44a773f3ad4bc9a016ab8011ad7cc1
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745438B2

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