Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate → (+/-)-tert-Butyl 4-((1-(3-bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

HRID 913877

반응식

HRID 913877 반응식
ClC(Cl)(Cl)C(=N)[O:4][CH:5]([C:7]1[CH:8]=[C:9]([Cl:25])[CH:10]=[C:11]2[C:15]=1[N:14]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[N:13]=[C:12]2[Br:24])[CH3:6].[F:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]2([CH2:49]O)[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]2)=[CH:32][CH:31]=1>ClCCl.C1CCCCC1>[Br:24][C:12]1[C:11]2[C:15](=[C:7]([CH:5]([O:4][CH2:49][C:36]3([C:33]4[CH:34]=[CH:35][C:30]([F:29])=[CH:31][CH:32]=4)[CH2:37][CH2:38][N:39]([C:42]([O:44][C:45]([CH3:46])([CH3:47])[CH3:48])=[O:43])[CH2:40][CH2:41]3)[CH3:6])[CH:8]=[C:9]([Cl:25])[CH:10]=2)[N:14]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:22])([CH3:23])[CH3:21])[N:13]=1

참가 물질

4

반응물 2

HCID 19084679Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylateHCID 57546223HCID 57546223, 화합물

생성물 1

HCID 57546087(+/-)-tert-Butyl 4-((1-(3-bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

시약·촉매·용매 1

HCID 21916607Dichloromethane cyclohexane용매

반응 조건

온도
0 °C

실험 절차

(±)-1-(3-Bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)ethyl 2,2,2-trichloroacetimidate (1.69 g, 3.07 mmol) and tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate (1.05 g, 3.38 mmol) were combined in a dichloromethane/cyclohexane mixture (1:1, 8 mL) and cooled to 0° C. The reaction was treated with tetrafluoroboric acid-diethyl ether complex (86 μL, 0.61 mmol), stirred at 0° C. for 1 h, quenched by addition of saturated sodium bicarbonate and diluted with diethyl ether. The layers were separated. The ethereal was washed with water (2×), brine (2×), dried over sodium sulfate, and concentrated. Column chromatography on silica gel (18% ethyl acetate/hexanes) gave 1.2 g (56%) as a white film. 1H-NMR (CDCl3, 500 MHz) δ 7.48 (d, J=1.84 Hz, 1H), 7.19-7.21 (m, 2H), 7.08 (m, 1H), 6.97-7.00 (m, 2H), 5.49-5.56 (m, 2H), 5.01 (q, J=6.1 Hz, 1H), 3.70 (m, 2H), 3.43-3.47 (m, 2H), 3.22 (m, 2H), 3.00-3.05 (m, 2H), 2.04-2.14 (m, 2H), 1.76-1.87 (m, 2H), 1.43 (s, 9H), 1.42 (m, 3H), 0.72-0.82 (m, 2H), 0.08 (s,9H). Mass spec.: 720.42 (MNa)+.

후처리

  1. additionThe reaction was treated with tetrafluoroboric acid-diethyl ether complex (86 μL, 0.61 mmol)
  2. customquenched by addition of saturated sodium bicarbonate
  3. additiondiluted with diethyl ether
  4. customThe layers were separated
  5. washThe ethereal was washed with water (2×), brine (2×)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customColumn chromatography on silica gel (18% ethyl acetate/hexanes) gave 1.2 g (56%) as a white film

출처 및 근거

ORD 기록
ord-34176bb58c674688b915c53d5606af45
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026257B2

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