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

HRID 501623

반응식

HRID 501623 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]

참가 물질

5

반응물 2

HCID 552549(Trifluoromethyl)trimethylsilaneHCID 16732142tert-Butyl-(2S,3R)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-formylpyrrolidine-1-carboxylate

생성물 1

HCID 16732286(2R,3R)-3-(tert-Butyl-dimethylsilanyloxy)-2-[(1R)-(2,2,2-trifluoro-1-hydroxyethyl)]pyrrolidine-1-carboxylic acid tert-butyl ester수율 46.7%

시약·촉매·용매 2

HCID 25953Cesium fluoride촉매HCID 313Hydrochloric Acid용매

실험 절차

To aldehyde 51C (2.10 g, 6.38 mmol) was added trimethyl(trifluoromethyl)silane (800 μL, 6.57 mmol) and cesium fluoride (dried under high vacuum at 130° C. for 12 h) (10.0 mg, 0.0658 mmol). The reaction was stirred at rt for 24 h then heated to 50° C. for 5 h. After cooling to rt, 4 N HCl (ca. 10 mL) was added and the reaction was stirred overnight. The brown aqueous solution was decanted and the waxy yellow solid was dried under high vacuum overnight then recrystallized from hexane to provide (2R,3R)-3-(tert-butyl-dimethyl-silanyloxy)-2-[(1R)-(2,2,2-trifluoro-1-hydroxy-ethyl)]-pyrrolidine-1-carboxylic acid tert-butyl ester (66A) (1.19 g) as a white solid. The mother liquor was concentrated and purified via flash chromatography eluting with 5-20% ethyl acetate/hexane to provide (2R,3R)-3-(tert-butyl-dimethyl-silanyloxy)-2-[(1S)-(2,2,2-trifluoro-1-hydroxy-ethyl)]-pyrrolidine-1-carboxylic acid tert-butyl ester (66B) (192 mg) as an oil and a mixture of 66A and starting material 51C (306 mg). The latter mixture was recrystallized from hexane to provide additional 66A (100 mg).

후처리

  1. temperaturethen heated to 50° C. for 5 h
  2. temperatureAfter cooling to rt
  3. stirringthe reaction was stirred overnight
  4. customThe brown aqueous solution was decanted
  5. customthe waxy yellow solid was dried under high vacuum overnight
  6. customthen recrystallized from hexane

출처 및 근거

ORD 기록
ord-c31db003c45841ada4f90e37e2b11255
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07772267B2

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