Sodium hydride → (S)-3-((tert-butyldimethylsilyl)oxy)-1-(4-(difluoromethyl)benzyl)pyrrolidin-2-one

HRID 1507270노트

반응식

HRID 1507270 반응식
[H-].[Na+].[Si:3]([O:10][C@H:11]1[CH2:15][CH2:14][NH:13][C:12]1=[O:16])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].Br[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH:25]([F:27])[F:26])=[CH:21][CH:20]=1>C1COCC1>[Si:3]([O:10][C@H:11]1[CH2:15][CH2:14][N:13]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([CH:25]([F:27])[F:26])=[CH:21][CH:20]=2)[C:12]1=[O:16])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 10584804(S)-3-((tert-Butyldimethylsilyl)oxy)pyrrolidin-2-oneHCID 575899071-(Bromomethyl)-4-(difluoromethyl)benzene

생성물 1

HCID 123626683(S)-3-((tert-butyldimethylsilyl)oxy)-1-(4-(difluoromethyl)benzyl)pyrrolidin-2-one수율 35%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A 60% dispersion of sodium hydride in mineral oil (232 mg, 5.31 mmol) was added to a stirred solution of (S)-3-((tert-butyldimethylsilyl)oxy)pyrrolidin-2-one (762 mg, 3.54 mmol) in THF (7 mL) at 0° C. After 15 min, a solution of 1-(bromomethyl)-4-(difluoromethyl)benzene (980 mg, 4.43 mmol) in THF (7 mL) was added to the reaction mixture. The resulting mixture was stirred at RT for 6 h. The reaction was quenched with pellets of ice. The resulting mixture was extracted with EtOAc. The combined organic layers were washed with water, dried over sodium sulfate, filtered and concentrated in vacuo. The crude reaction mixture was purified using silica gel column chromatography (0-30% EtOAc/hexanes) to afford (S)-3-((tert-butyldimethylsilyl)oxy)-1-(4-(difluoromethyl)benzyl)pyrrolidin-2-one (440 mg, 35% yield) as a white solid: LCMS (M+H)+356.3; 1H NMR (500 MHz, chloroform-d) δ 7.49 (d, J=8.1 Hz, 2H), 7.35 (d, J=7.9 Hz, 2H), 6.65 (br. t, J=1.0 Hz, 1H), 4.56-4.44 (m, 2H), 4.38 (t, J=7.5 Hz, 1H), 3.27 (ddd, J=9.7, 8.7, 3.4 Hz, 1H), 3.13 (dt, J=9.7, 7.4 Hz, 1H), 2.36-2.27 (m, 1H), 1.98-1.90 (m, 1H), 0.96 (br. s., 9H), 0.22-0.20 (m, 3H), 0.20-0.18 (m, 3H).

후처리

  1. customThe reaction was quenched with pellets of ice
  2. extractionThe resulting mixture was extracted with EtOAc
  3. washThe combined organic layers were washed with water
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude reaction mixture
  8. customwas purified

출처 및 근거

ORD 기록
ord-ad01aefeb1064d6bbdb73fd4235ae3fc
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221796B2

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