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

HRID 1864701노트

반응식

HRID 1864701 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 (2S,3S)-3-(tert-butyldimethylsilanyloxy)-2-formylpyrrolidine-1-carboxylic acid tert-butyl ester (5B) (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% EtOAc/hexane to provide (2R,3S)-3-(tert-butyldimethylsilanyloxy)-2-[(1R)-(2,2,2-trifluoro-1-hydroxy-ethyl)]-pyrrolidine-1-carboxylic acid tert-butyl ester (5C) (357 mg) as a colorless oil and (2R,3S)-3-(tert-butyldimethylsilanyloxy)-2-[(1S)-(2,2,2-trifluoro-1-hydroxy-ethyl)]-pyrrolidine-1-carboxylic acid tert-butyl ester (5D) (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% EtOAc/hexane

출처 및 근거

ORD 기록
ord-f53497d9ee8e469d9158c4bd89cfae1c
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07625923B2

반응 노트

불러오는 중…