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

HRID 1018230

反応式

HRID 1018230 の反応式
[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

参加物

5

反応物 2

HCID 5207692-(Trifluoromethyl)oxirane2 回HCID 10936948N-(3-phenoxyphenyl)[[3-(1,1-dimethylethoxy)phenyl]methyl]amine

生成物 1

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

試薬・触媒・溶媒 2

HCID 2733225Ytterbium triflate触媒HCID 6342Acetonitrile溶媒2 回

反応条件

温度
45 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-81d69d323a514dd3bb3ee94064d97c1e
出典データセット
uspto-grants-2002_11
特許番号
US06479552B2

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