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Methyl iodide → tert-butyl 4-((2-(((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-4-(trifluoromethyl)phenyl)(methoxy)methyl)piperidine-1-carboxylate

HRID 2075047
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HRID 2075047 반응식
[F:1][C:2]([F:48])([F:47])[C:3]1[CH:4]=[C:5]([CH:40]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:42]=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[CH:25]([OH:39])[CH:26]1[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]1)[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.[H-].[Na+].[CH3:51]I>C1COCC1>[F:44][C:43]([F:46])([F:45])[C:41]1[CH:40]=[C:5]([CH:4]=[C:3]([C:2]([F:47])([F:1])[F:48])[CH:42]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:22])([F:23])[F:24])[CH:18]=[CH:17][C:16]=1[CH:25]([O:39][CH3:51])[CH:26]1[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]1)[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58968740tert-butyl 4-((2-(((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-4-(trifluoromethyl)phenyl)(hydroxy)methyl)piperidine-1-carboxylate

생성물 1

HCID 58968718tert-butyl 4-((2-(((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-4-(trifluoromethyl)phenyl)(methoxy)methyl)piperidine-1-carboxylate수율 72.6%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of tert-butyl 4-((2-(((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-4-(trifluoromethyl)phenyl)(hydroxy)methyl)piperidine-1-carboxylate (62.2 mg, 0.089 mmol) in THF at 0° C. was added sodium hydride (10.7 mg, 0.27 mmol). The mixture was stirred at room temperature for 30 minutes, cooled to 0° C. and methyl iodide (30 μL, 0.5 mmol) was added. The mixture was stirred at room temperature overnight. The reaction was quenched with methanol. Solvent was removed and the residue was purified by chromatography over 12+S Biotage silica column (eluted with 0-30% ethyl acetate in hexanes) to afford the title compound (45.9 mg, 72%). 1H NMR (400 MHz, CDCl3) δ ppm 1.09-1.16 (m, 1H) 1.17-1.29 (m, 2H) 1.43 (s, 9H) 1.58-1.69 (m, 1H) 1.84 (d, J=13.28 Hz, 1H) 2.44-2.58 (m, 2H) 3.04 (s, 3H) 4.04 (d, J=12.45 Hz, 1H) 4.11 (d, J=7.47 Hz, 1H) 4.15 (d, J=7.05 Hz, 1H) 4.20 (s, 3H) 4.68 (d, J=15.77 Hz, 1H) 4.71 (s, 2H) 4.88 (d, J=16.18 Hz, 1H) 7.36 (s, 1H) 7.50 (d, J=8.30 Hz, 1H) 7.57 (d, J=7.88 Hz, 1H) 7.65 (s, 2H) 7.78 (s, 1H). MS (ES+) Calc: 710.3, Found: 711.6 (M+1)

후처리

  1. temperaturecooled to 0° C.
  2. stirringThe mixture was stirred at room temperature overnight
  3. customThe reaction was quenched with methanol
  4. customSolvent was removed
  5. customthe residue was purified by chromatography over 12+S Biotage silica column (eluted with 0-30% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-de96337b72b04e2fbf4f209046b235d3
출처 데이터셋
uspto-grants-2011_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07919506B2

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