Lithium Hexamethyldisilazide → tert-Butyl 1,3-thiazol-4-yl[(2,4,5-trifluorophenyl)sulfonyl]carbamate

HRID 46321

반응식

HRID 46321 반응식
[S:1]1[CH:5]=[C:4]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[N:3]=[CH:2]1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[F:24][C:25]1[CH:30]=[C:29]([F:31])[C:28]([F:32])=[CH:27][C:26]=1[S:33](Cl)(=[O:35])=[O:34]>O1CCCC1>[S:1]1[CH:5]=[C:4]([N:6]([S:33]([C:26]2[CH:27]=[C:28]([F:32])[C:29]([F:31])=[CH:30][C:25]=2[F:24])(=[O:35])=[O:34])[C:7](=[O:13])[O:8][C:9]([CH3:10])([CH3:12])[CH3:11])[N:3]=[CH:2]1

참가 물질

5

반응물 3

HCID 2733832Lithium HexamethyldisilazideHCID 27769792,4,5-Trifluorobenzenesulfonyl chlorideHCID 53241636tert-butyl N-(1,3-thiazol-4-yl)carbamate

생성물 1

HCID 59436528tert-Butyl 1,3-thiazol-4-yl[(2,4,5-trifluorophenyl)sulfonyl]carbamate수율 64%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

To a solution of tert-butyl 1,3-thiazol-4-ylcarbamate (Preparation 72, 28.94 g, 144.55 mmol) in anhydrous tetrahydrofuran (600 ml), cooled to −70° C., under nitrogen was added lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (1 M in tetrahydrofuran, 144.55 ml, 144.55 mmol) dropwise. The reaction mixture was warmed to room temperature and stirred for 1 hour before cooling −70° C. 2,4,5-trifluoro benzenesulfonyl chloride (40 g, 173.46 mmol) in tetrahydrofuran (80 ml) was added dropwise and then the reaction mixture was slowly warmed to room temperature and stirred for 2 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. Organic layer was washed with water and saturated aqueous sodium chloride solution before concentrating in vacuo. The crude residue was purified by column chromatography eluting with ethyl acetate:hexane (gradient 1:19 to 3:17, by volume) to afford the title compound as white solid, 37 g, 64% yield.

후처리

  1. temperaturebefore cooling −70° C
  2. temperaturethe reaction mixture was slowly warmed to room temperature
  3. stirringstirred for 2 hours
  4. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution
  5. extractionextracted with ethyl acetate
  6. washOrganic layer was washed with water and saturated aqueous sodium chloride solution
  7. concentrationbefore concentrating in vacuo
  8. customThe crude residue was purified by column chromatography
  9. washeluting with ethyl acetate

출처 및 근거

ORD 기록
ord-287903f791514e21aae51f2f2cf1ca67
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541588B2

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