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

HRID 913887
ノート
印刷プレビュー

反応式

HRID 913887 の反応式
ClC(Cl)(Cl)C(=N)O[CH:5]([C:7]1[C:15]2[C:11](=[CH:12][N:13]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[N:14]=2)[CH:10]=[C:9]([Cl:24])[CH:8]=1)[CH3:6].[F:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]2([CH2:48][OH:49])[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH2:36]2)=[CH:31][CH:30]=1>ClCCl.C1CCCCC1>[Cl:24][C:9]1[CH:8]=[C:7]([CH:5]([O:49][CH2:48][C:35]2([C:32]3[CH:31]=[CH:30][C:29]([F:28])=[CH:34][CH:33]=3)[CH2:36][CH2:37][N:38]([C:41]([O:43][C:44]([CH3:45])([CH3:46])[CH3:47])=[O:42])[CH2:39][CH2:40]2)[CH3:6])[C:15]2[C:11](=[CH:12][N:13]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:22])([CH3:21])[CH3:23])[N:14]=2)[CH:10]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

4

反応物 2

HCID 19084679Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylateHCID 57546188(+/-)-1-(5-Chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethyl 2,2,2-trichloroacetimidate

生成物 1

HCID 57546145(+/-)-tert-Butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-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-(5-Chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethyl 2,2,2-trichloroacetimidate (1.1 g, 2.33 mmol) and tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate (0.79 g, 2.57 mmol) were combined in a dichloromethane/cyclohexane mixture (1:1, 10 mL) and cooled to 0° C. The reaction was treated with tetrafluoroboric acid-diethyl ether complex (64 μL, 0.47 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 (20% ethyl acetate/hexanes) gave 0.81 g (56%) as a clear film. 1H-NMR (CDCl3, 500 MHz) δ 8.00 (s, 1H), 7.49 (d, J=1.8 Hz, 1H), 7.30-7.33 (m, 2H), 7.01-7.05 (m, 2H), 6.77 (m, 1H), 5.62-5.68 (s, 2H), 4.93 (q, J=6.4 Hz, 1H), 3.72 (m, 2H), 3.58-3.61 (m, 2H), 3.33-3.39 (m, 2H), 3.03-3.08 (m, 2H), 2.08-2.22 (m, 2H), 1.87-1.97 (m, 2H), 1.44 (s, 9H), 1.43 (d, J=6.4 Hz, 3H), 0.91-0.92 (m, 2H), 0.05 (s, 9H). Mass spec.: 618.86 (MH)+.

後処理

  1. additionThe reaction was treated with tetrafluoroboric acid-diethyl ether complex (64 μL, 0.47 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 (20% ethyl acetate/hexanes) gave 0.81 g (56%) as a clear film

出典と根拠

ORDレコード
ord-5360ac0f9fc54674812126238aca631f
出典データセット
uspto-grants-2011_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08026257B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート