Cesium fluoride → (2R,3S)-3-(tert-Butyl-dimethylsilanyloxy)-2-[(1S)-(2,2,2-trifluoro-1-hydroxyethyl)]pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 501641노트

반응식

HRID 501641 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[CH:21]=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si](C)(C)[C:25]([F:28])([F:27])[F:26].[F-].[Cs+]>Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[C@@H:21]([OH:22])[C:25]([F:28])([F:27])[F:26])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[C@H:21]([OH:22])[C:25]([F:28])([F:27])[F:26])=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

6

반응물 3

HCID 25953Cesium fluorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 16731848(2S,3S)-tert-Butyl 3-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylate

생성물 2

HCID 16731517(2R,3S)-3-(tert-Butyl-dimethylsilanyloxy)-2-[(1S)-(2,2,2-trifluoro-1-hydroxyethyl)]pyrrolidine-1-carboxylic acid tert-butyl esterHCID 16732287(2R,3S)-3-(tert-Butyl-dimethylsilanyloxy)-2-[(1R)-(2,2,2-trifluoro-1-hydroxyethyl)]pyrrolidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 313Hydrochloric Acid용매

실험 절차

To 75A (1.00 g, 3.04 mmol) was added trimethyl(trifluoromethyl)silane (550 mg, 3.87 mmol) and cesium fluoride (10 mg, dried under high vacuum at 130° C. for 12 h). The mixture was stirred at rt for 24 h, and then was heated to 50° C. for 5 h. After cooling to rt, 4N HCl (ca. 10 mL) was added and the reaction was stirred overnight. The product was extracted with EtOAc (3×30 mL). The organic layer was washed with saturated aqueous NaHCO3 and brine, then dried (MgSO4), filtered and concentrated. The residue was purified via flash chromatography eluting with 0-15% ethyl acetate/hexane to provide (2R,3S)-3-(tert-butyl-dimethyl-silanyloxy)-2-[(1R)-(2,2,2-trifluoro-1-hydroxy-ethyl)]-pyrrolidine-1-carboxylic acid tert-butyl ester (75B) (357 mg) as a colorless oil and (2R,3S)-3-(tert-butyl-dimethylsilanyloxy)-2-[(1S)-(2,2,2-trifluoro-1-hydroxyethyl)]pyrrolidine-1-carboxylic acid tert-butyl ester (75C) (380 mg) as a white solid.

후처리

  1. temperaturewas heated to 50° C. for 5 h
  2. temperatureAfter cooling to rt
  3. stirringthe reaction was stirred overnight
  4. extractionThe product was extracted with EtOAc (3×30 mL)
  5. washThe organic layer was washed with saturated aqueous NaHCO3 and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified via flash chromatography
  10. washeluting with 0-15% ethyl acetate/hexane

출처 및 근거

ORD 기록
ord-73116605375d4b4c9e1ef018c4f03d1a
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07772267B2

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