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

HRID 50496노트

반응식

HRID 50496 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
40 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-3c6dbc13252c4f089520c2c5ea591873
출처 데이터셋
uspto-grants-2004_03
특허 번호
US06710089B2

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