Water → (S)-(3,5-Bis-trifluoromethyl-benzyl)-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amine

HRID 2075022노트

반응식

HRID 2075022 반응식
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1[C@H:25]([CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[OH:26])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.[H-].[Na+].[CH3:44]I.O>C1COCC1>[F:41][C:2]([F:1])([F:40])[C:3]1[CH:4]=[C:5]([CH:33]=[C:34]([C:36]([F:37])([F:38])[F:39])[CH:35]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1[C@H:25]([CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[O:26][CH3:44])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58968644(S)-(2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-cyclohexyl-methanol

생성물 1

HCID 58968607(S)-(3,5-Bis-trifluoromethyl-benzyl)-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amine수율 96%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of (S)-(2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-cyclohexyl-methanol (1.81 g, 3.04 mmol) in THF (20 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil, 254.4 mg, 6.4 mmol). The mixture was stirred at room temperature for 30 minutes, cooled to 0° C. and methyl iodide (1.31 g, 9.2 mmol) was added. The mixture was stirred at room temperature for 5 hours. Water (10 mL) was added and the mixture was extracted with ethyl acetate. Combined organic layers were washed with brine, dried with sodium sulfate and concentrated in vacuo. The residue was purified by chromatography over 25+M Biotage silica column (eluted with 0-30% ethyl acetate in heptane) to afford the title compound as a colorless oil (1.77 g, 96%). 1H NMR (400 MHz, CDCl3) δ ppm 0.93-1.14(m, 5H) 1.18 (d, J=10.79 Hz, 1H) 1.43-1.54(m, 1H) 1.59-1.65(m, J=4.56 Hz, 2H) 1.68-1.74 (m, J=2.49 Hz, 1H) 1.90 (d, J=12.03 Hz, 1H) 3.06 (s, 3H) 4.08 (d, J=7.05 Hz, 1H) 4.21 (s, 3H) 4.71 (d, J=15.77 Hz, 1H) 4.71 (s, 2H) 4.88 (d, J=16.18 Hz, 1H) 7.35 (s, 1H) 7.49 (d, J=8.30 Hz, 1H) 7.55 (d, J=8.30 Hz, 1H) 7.66 (s, 2H) 7.78 (s, 1H). MS (ES+) Calc: 609.2, Found: 610.5 (M+1). [α]D20=36.49 deg (c=10.05 mg/mL, acetone) Determination of absolute configuration of (S)-(3,5-bis-trifluoromethyl-benzyl)-[2-(cyclohexyl-methoxymethyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amine

후처리

  1. temperaturecooled to 0° C.
  2. stirringThe mixture was stirred at room temperature for 5 hours
  3. extractionthe mixture was extracted with ethyl acetate
  4. washCombined organic layers were washed with brine
  5. dry with materialdried with sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by chromatography over 25+M Biotage silica column (eluted with 0-30% ethyl acetate in heptane)

출처 및 근거

ORD 기록
ord-1904f5db208f41629577e2066f8e37ea
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07919506B2

반응 노트

불러오는 중…