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

反応式

HRID 913877 の反応式
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

参加物

4

反応物 2

HCID 19084679Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylateHCID 57546223HCID 57546223、化合物

生成物 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

試薬・触媒・溶媒 1

HCID 21916607Dichloromethane cyclohexane溶媒

反応条件

温度
0 °C

実験手順

(±)-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)+.

後処理

  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

出典と根拠

ORDレコード
ord-34176bb58c674688b915c53d5606af45
出典データセット
uspto-grants-2011_09
特許番号
US08026257B2

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