2-(Trifluoromethyl)oxirane → 3-[(3-phenoxyphenyl)-[[4-(N,N-diethylamino)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol

HRID 50496ノート

反応式

HRID 50496 の反応式
[O:1]([C:8]1[CH:9]=[C:10]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])=[CH:18][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.FC(F)(F)S([O-])(=O)=O.[Yb+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>C(#N)C>[O:1]([C:8]1[CH:9]=[C:10]([N:14]([CH2:15][C:16]2[CH:17]=[CH:18][C:19]([N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])=[CH:20][CH:21]=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 3

HCID 5207692-(Trifluoromethyl)oxiraneHCID 2733225Ytterbium triflateHCID 86588543(3-phenoxyphenyl)[4-(N,N-diethylamino)phenyl]methylamine

生成物 1

HCID 235060693-[(3-phenoxyphenyl)-[[4-(N,N-diethylamino)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol収率 17.4%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
40 °C

実験手順

The 3-[(3-phenoxyphenyl)[4-(N,N-diethylamino)phenyl]methylamine (0.69 g, 2.0 mmol) product from EX-631A and 1,1,1-trifluoro-2,3-epoxypropane (0.45 g, 4 mmol) were dissolved in 1 mL of acetonitrile. Ytterbium (III) trifluoromethanesulfonate (0.12 g, 0.1 mmol) was added, and the stirred solution was warmed to 40° C. for 4 h, at which time HPLC analysis indicated that no secondary amine starting material remained. The reaction was quenched with water and extracted with ether. The ether layer was washed with water and brine, then dried over MgSO4. The crude product was purified by flash column chromatography on silica gel eluting with 1:7:0.01 ethyl acetate: hexane:ammonium hydroxide followed by reverse phase preparative HPLC eluting with 10% to 90% acetonitrile in water to give 160 mg (17%) of the desired 3-[(3-phenoxyphenyl)-[[4-(N,N-diethylamino)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol product as a yellow oil, >95% pure by HPLC analysis. 1H NMR (CD30D) δ 7.39 (d, 2H), 7.31 (d, 2H), 7.22 (m, 3H), 7.13 (d, 1H), 6.98 (t, 1H), 6.75 (dd, 2H), 6.47 (dd, 1H), 6.20 (d, 1H), 4.03 (m, 1H), 3.90 (s, 2H), 3.58 (m, 4H), 3.36 (dd, 1H), 3.12 (dd, 1H), 1.05 (t, 6H). 19F NMR (CD30D) δ −80.51 (d, 3F). HRMS calcd. 459.2259 M+H]+, found: 459.2250.

後処理

  1. customThe reaction was quenched with water
  2. extractionextracted with ether
  3. washThe ether layer was washed with water and brine
  4. dry with materialdried over MgSO4
  5. customThe crude product was purified by flash column chromatography on silica gel eluting with 1:7:0.01 ethyl acetate
  6. washeluting with 10% to 90% acetonitrile in water

出典と根拠

ORDレコード
ord-3c6dbc13252c4f089520c2c5ea591873
出典データセット
uspto-grants-2004_03
特許番号
US06710089B2

反応ノート

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