Imidazole → Tert-butyl{[4'-fluoro-5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methoxy}dimethylsilane

HRID 1028626노트

반응식

HRID 1028626 반응식
[Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N1C=CN=C1.[F:14][C:15]1[C:20]([CH:21]([CH3:23])[CH3:22])=[CH:19][C:18]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][C:25]=2[CH2:34][OH:35])=[C:17]([O:36][CH3:37])[CH:16]=1.O>C(Cl)Cl>[C:4]([Si:1]([O:35][CH2:34][C:25]1[CH:26]=[C:27]([C:30]([F:32])([F:33])[F:31])[CH:28]=[CH:29][C:24]=1[C:18]1[CH:19]=[C:20]([CH:21]([CH3:23])[CH3:22])[C:15]([F:14])=[CH:16][C:17]=1[O:36][CH3:37])([CH3:3])[CH3:2])([CH3:7])([CH3:6])[CH3:5]

참가 물질

6

반응물 4

HCID 795ImidazoleHCID 962WaterHCID 28928tert-Butyldimethylsilyl chlorideHCID 533638284'-Fluoro-2'-methoxy-5'-(1-methylethyl)-4-(trifluoromethyl)(1,1'-biphenyl)-2-methanol

생성물 1

HCID 66717161Tert-butyl{[4'-fluoro-5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methoxy}dimethylsilane

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

tert-Butyldimethylsilyl chloride (0.48 g, 3.21 mmol) and imidazole (0.50 g, 7.30 mmol) were added successively to a stirred solution of [4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanol (1.00 g, 2.93 mmol) in dry CH2Cl2 (13.4 mL) at room temperature under N2 and the reaction was stirred overnight. Water (50 mL) was added and the mixture was extracted with EtOAc (3×50 mL). The combined extracts were dried (MgSO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 25×160 mm, 1% EtOAc in hexanes) to afford tert-butyl {[4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methoxy}dimethylsilane as a colorless oil. Rf=0.16 (1% EtOAc in hexanes). LCMS calc.=457.2; found=457.2 (M+1)+. 1H NMR (500 MHz, CDCl3) δ 7.94 (s, 1H), 7.57 (d, J=7.8 Hz, 1H), 7.29 (d, J=7.6 Hz, 1H), 7.00 (d, J=8.6 Hz, 1H), 6.69 (d, J=12.1 Hz, 1H), 4.63 (br s, 1H), 4.50 (br s, 1H), 3.75 (s, 3H), 3.29-3.21 (m, 1H), 1.28 (d, J=6.9 Hz, 6H), 0.93 (s, 9H), 0.03 (s, 6H).

후처리

  1. extractionthe mixture was extracted with EtOAc (3×50 mL)
  2. dry with materialThe combined extracts were dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customto give the crude product
  5. customThis was purified by flash chromatography (Si, 25×160 mm, 1% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-04f0f67e5b6b4c409f927da08971b42f
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08735435B2

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