2-(Trifluoromethyl)oxirane → 3-((3-Tert-butoxybenzyl)(3-phenoxyphenyl)amino)-1,1,1-trifluoropropan-2-ol

HRID 1018230

반응식

HRID 1018230 반응식
[O:1]([C:8]1[CH:9]=[C:10]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH:17]=2)[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:27][C:28]([F:33])([F:32])[CH:29]1[O:31][CH2:30]1>C(#N)C.[O-]S(C(F)(F)F)(=O)=O.[Yb+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O>[O:1]([C:8]1[CH:9]=[C:10]([N:14]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH:17]=2)[CH2:30][CH:29]([OH:31])[C:28]([F:33])([F:32])[F:27])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

5

반응물 2

HCID 5207692-(Trifluoromethyl)oxirane2회HCID 10936948N-(3-phenoxyphenyl)[[3-(1,1-dimethylethoxy)phenyl]methyl]amine

생성물 1

HCID 117332173-((3-Tert-butoxybenzyl)(3-phenoxyphenyl)amino)-1,1,1-trifluoropropan-2-ol수율 42%

시약·촉매·용매 2

HCID 2733225Ytterbium triflate촉매HCID 6342Acetonitrile용매2회

반응 조건

온도
45 °C

실험 절차

The N-(3-phenoxyphenyl)[[3-(1,1-dimethylethoxy)phenyl]methyl]amine (0.270 g, 0.78 mmol) product from EX-654B was dissolved in 2 mL of acetonitrile. Ytterbium triflate (16 mg, 0.026 mmol) was added in 0.5 mL of acetonitrile, and the mixture was stirred under nitrogen. 1,1,1-Trifluoro-2,3-epoxypropane (0.105 g, 0.94 mmol) was added, the vial was sealed and heated to 45° C. After 24 h, TLC analysis showed 50% conversion, so additional 1,1,1-trifluoro-2,3-epoxypropane (88.6 mg, 0.79 mmol) was added and heating continued for an additional 24 h. The resulting mixture was eluted from silica gel with an ethyl acetate in hexane gradient (1.5-7% ethyl acetate). Fractions were pooled based on TLC analysis to give 150 mg (42%) of the desired 3-[(3-phenoxy-phenyl)[[3-(1,1-dimethylethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol product as a clear, colorless oil, and an additional 60 mg (17%) was obtained as an amber oil. HRMS calcd. for C26H28F3NO3: 460.2100 [M+H]+, found: 460.2103. 1H NMR (C6D6) δ6.78-7.08 (m, 9H), 6.68 (d, 1H), 6.55 (t, 1H), 6.43 (dd, 1H), 6.34 (dd, 1H), 4.23 (s, 2H), 3.81 (m, 1H), 3.48 (dd, 1H), 3.24 (m, 1H), 2.25 (br s, 1H), 1.07 (s, 9H). 19F NMR (C6D6) δ−78.92 (d, 3F).

후처리

  1. customthe vial was sealed
  2. additionwas added
  3. temperatureheating
  4. waitcontinued for an additional 24 h
  5. washThe resulting mixture was eluted from silica gel with an ethyl acetate in hexane gradient (1.5-7% ethyl acetate)

출처 및 근거

ORD 기록
ord-81d69d323a514dd3bb3ee94064d97c1e
출처 데이터셋
uspto-grants-2002_11
특허 번호
US06479552B2

연결된 노트

불러오는 중…