2-(Trifluoromethyl)oxirane → 3-[[3-(4-Fluorophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol

HRID 50503

反応式

HRID 50503 の反応式
[F:1][C:2]1[CH:29]=[CH:28][C:5]([O:6][C:7]2[CH:8]=[C:9]([NH:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([O:21][C:22]([F:27])([F:26])[CH:23]([F:25])[F:24])[CH:16]=3)[CH:10]=[CH:11][CH:12]=2)=[CH:4][CH:3]=1.[F:30][C:31]([F:36])([F:35])[CH:32]1[O:34][CH2:33]1>C(#N)C.FC(F)(F)S([O-])(=O)=O.[Yb+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[CH:8]=[C:9]([N:13]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([O:21][C:22]([F:26])([F:27])[CH:23]([F:24])[F:25])[CH:16]=3)[CH2:33][CH:32]([OH:34])[C:31]([F:36])([F:35])[F:30])[CH:10]=[CH:11][CH:12]=2)=[CH:28][CH:29]=1

参加物

5

反応物 2

HCID 5207692-(Trifluoromethyl)oxiraneHCID 23505995N-[3-(4fluorophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amine

生成物 1

HCID 102298083-[[3-(4-Fluorophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol収率 81%

試薬・触媒・溶媒 2

HCID 2733225Ytterbium triflate触媒HCID 6342Acetonitrile溶媒

反応条件

温度
40 °C

実験手順

The N-[3-(4-fluorophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amine (612 mg, 1.5 mmol) product from EX-634C and 1,1,1-trifluoro-2,3-epoxypropane (268 mg, 2.4 mmol) were dissolved in 1.0 mL of acetonitrile. Ytterbium (III) trifluoromethanesulfonate (43 mg, 0.07 mmol) was added, and the stirred solution was warmed to 40° C. for 2.5 h under an atmosphere of nitrogen, 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 brine and water, then dried over anhydrous MgSO4. The ether was removed in vacuo, and the crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate in hexane (1:11) to give 633 mg (81%) of the desired 3-[[3-(4-fluorophenoxy)phenyl][[3-(1,1,2,2-tetrafluoro-ethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol product as a yellow oil, 99% pure by HPLC analysis. 1H NMR (CDCl3) δ 7.35 (t, 1H), 7.15 (m, 3H), 6.98 (m, 5H), 6.49 (dd, 1H), 6.38 (dd, 1H), 6.33 (m, 1H), 5.92 (tt, 1H), 4.67 (ABq, 2H), 4.37 (m, 1H), 3.91 (dd, 11H), 3.59 (dd, 1H), 2.48 (d, 1H). 19F NMR (CDCl3) δ −79.2 (d, 3F), −88.5 (m, 2F), −120.33 (m, 1F), −137.2 (dt, 2F). HRMS calcd. for C24H19F8NO3:522.1315 [M+H]+, found: 522.1297.

後処理

  1. customThe reaction was quenched with water
  2. extractionextracted with ether
  3. washThe ether layer was washed with brine and water
  4. dry with materialdried over anhydrous MgSO4
  5. customThe ether was removed in vacuo
  6. customthe crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate in hexane (1:11)

出典と根拠

ORDレコード
ord-052d860469244c009ad1a26f093997a3
出典データセット
uspto-grants-2004_03
特許番号
US06710089B2

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