Hydrochloric Acid → 2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-thiazol-5-ylethanol

HRID 244488

반응식

HRID 244488 반응식
C[Si](C)(C)[C:3]1[S:4][CH:5]=[CH:6][N:7]=1.[Li]CCCC.[F:15][C:16]([F:36])([F:35])[C:17]([C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[N:24]([C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=1)[N:23]=[CH:22]2)=[O:18].Cl>CCOCC.C1COCC1>[F:36][C:16]([F:15])([F:35])[C:17]([C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[N:24]([C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=1)[N:23]=[CH:22]2)([C:5]1[S:4][CH:3]=[N:7][CH:6]=1)[OH:18]

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 5884532-TrimethylsilylthiazoleHCID 57943269HCID 57943269, 화합물HCID 178418339Butyllithium

생성물 1

HCID 594372042,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-thiazol-5-ylethanol

시약·촉매·용매 2

HCID 3283Diethyl Ether용매2회HCID 8028Tetrahydrofuran용매

실험 절차

To a chilled (−78° C.) solution of 2-trimethylsilanyl-thiazole (157 mg, 1.00 mmol) in dry ether (2 mL) was added n-BuLi (440 μL, 2.5 M in hexanes, 1.10 mmol). After 30 minutes, a solution of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone (154 mg, 0.50 mmol) in dry ether (2 mL) was added. After 1 hour, the mixture was warmed to room temperature, quenched with 10 mL of saturated aqueous sodium bicarbonate and extracted with three 10 mL portions of ethyl ether. The combined organic layers was washed with 10 mL of brine, dried over sodium sulfate, filtered, and concentrated in vacuo to give 202 mg of the crude product. To a solution of crude product (100 mg) in THF (2 mL) was added 2 M HCl (1 mL) and the mixture was stirred overnight. The mixture was then quenched with 10 mL of saturated aqueous sodium bicarbonate and extracted with three 10 mL portions of ethyl acetate. The combined organic layers were washed with brine (10 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. The mixture was purified over SiO2 using ethyl acetate-hexanes (0-100% gradient) to afford 38.4 mg (39% over two steps) of the title compound. MS m/z 394.26 (MH+).

후처리

  1. waitAfter 1 hour
  2. customquenched with 10 mL of saturated aqueous sodium bicarbonate
  3. extractionextracted with three 10 mL portions of ethyl ether
  4. washThe combined organic layers was washed with 10 mL of brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give 202 mg of the crude product
  9. customThe mixture was then quenched with 10 mL of saturated aqueous sodium bicarbonate
  10. extractionextracted with three 10 mL portions of ethyl acetate
  11. washThe combined organic layers were washed with brine (10 mL)
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe mixture was purified over SiO2

출처 및 근거

ORD 기록
ord-e47e56ad943d4caaab20df3e904c0f6a
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658637B2

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