Sodium hydride → tert-Butyl 4-phenyl-4-(((5-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)methoxy)methyl)piperidine-1-carboxylate

HRID 913811노트

반응식

HRID 913811 반응식
[OH:1][CH2:2][C:3]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.Br[CH2:23][C:24]1[CH:25]=[C:26]([C:41]([F:44])([F:43])[F:42])[CH:27]=[C:28]2[C:32]=1[N:31]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[N:30]=[CH:29]2.[H-].[Na+]>CN(C)C=O>[C:16]1([C:3]2([CH2:2][O:1][CH2:23][C:24]3[CH:25]=[C:26]([C:41]([F:44])([F:42])[F:43])[CH:27]=[C:28]4[C:32]=3[N:31]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:38])([CH3:39])[CH3:40])[N:30]=[CH:29]4)[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:14])([CH3:15])[CH3:13])=[O:10])[CH2:5][CH2:4]2)[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateHCID 575460807-(Bromomethyl)-5-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole

생성물 1

HCID 57545920tert-Butyl 4-phenyl-4-(((5-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)methoxy)methyl)piperidine-1-carboxylate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
0 °C

실험 절차

To a solution of tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (0.669 g, 2.3 mmol) and 7-(bromomethyl)-5-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (0.94 g, 2.3 mmol) in dimethylformamide (7 mL) at 0° C. was added sodium hydride (60% in mineral oil, 0.119 g, 3.0 mmol). The resulting solution was stirred at 0° C. for 30 min. The reaction was quenched by the cautious addition of saturated ammonium chloride and diluted with diethyl ether. The ethereal was washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (12% EtOAc/Hex) gave 1.13 g (79%) as an oil. 1H-NMR (CDCl3, 500 MHz) δ 8.03 (s, 1H), 7.98 (s, 1H), 7.41 (d, J=0.9 Hz, 1H), 7.10-7.28 (m, 5H), 5.37 (s, 2H), 4.73 (s, 2H), 3.69 (bs, 2H), 3.45 (s, 2H), 3.39 (m, 2H), 3.01 (m, 2H), 2.13 (m, 2H), 1.77 (m, 2H), 1.41 (s, 9H), 0.77 (m, 2H), −0.11 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 155.0 142.7, 139.3, 134.7, 128.4, 127.1, 126.4, 125.6, 124.8, 124.6 (q, J=273 Hz), 123.5 (q, J=32 Hz), 122.1, 119.2, 79.4, 79.2, 79.0, 70.6, 66.1, 41.5, 40.3 (br), 32.2, 28.5, 17.8, −1.4. Mass spec.: 620.15 (MH)+.

후처리

  1. customThe reaction was quenched by the cautious addition of saturated ammonium chloride
  2. additiondiluted with diethyl ether
  3. washThe ethereal was washed with water (2×)
  4. dry with materialbrine, dried over magnesium sulfate
  5. concentrationconcentrated
  6. customColumn chromatography (12% EtOAc/Hex) gave 1.13 g (79%) as an oil

출처 및 근거

ORD 기록
ord-51ae9b02823a4b4a84a91acc2976b6f1
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026257B2

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