4-Bromopyrazole → tert-Butyl 4-(4-bromo-1H-pyrazol-1-yl)piperidine-1-carboxylate

HRID 216715ノート

反応式

HRID 216715 の反応式
[H-].[Na+].[Br:3][C:4]1[CH:5]=[N:6][NH:7][CH:8]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19](OS(C)(=O)=O)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10]>CN(C=O)C>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([N:6]2[CH:5]=[C:4]([Br:3])[CH:8]=[N:7]2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

参加物

5

反応物 3

HCID 163754-BromopyrazoleHCID 24758Sodium hydrideHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidine

生成物 1

HCID 45480278tert-Butyl 4-(4-bromo-1H-pyrazol-1-yl)piperidine-1-carboxylate

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

NaH (60% in mineral oil, 1.36 g, 34 mmol) is added portionwise to a stirred solution of 4-bromopyrazole (4.58 g, 30.9 mmol) in DMF (20 ml). The resulting mixture is stirred for 1 h at 0° C. and 4-Methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (as obtained in preparation 61, 8.62 g, 30.9 mmol) is added. The resulting pale suspension is heated at 100° C. for 1 h. The reaction is quenched with water and extracted with EtOAc several times. The combined organic layers are washed with brine, dried over Na2SO4, filtered and the filtrate is concentrated in vacuo. The residue is purified by chromatography on a 120 g silica gel column on a Combiflash Companion™ (Isco Inc.) apparatus (gradient hexanes: TBDME from 1:0=>0:1) to afford the title compound as a colorless solid, Rt=1.213 min (Acquity HPLC BEH C18, 2.1×50 mm, 1.7 micron, detection 215 nM, 0.1 min 2% CH3CN in H2O, 2% to 100% CH3CN in H2O in 1.5 min, 0.4 min 100% CH3CN+0.1% TFA, flow rate 1.0 ml/min); MS: 330 (M+1, 79Br)+.

後処理

  1. temperatureThe resulting pale suspension is heated at 100° C. for 1 h
  2. customThe reaction is quenched with water
  3. extractionextracted with EtOAc several times
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate is concentrated in vacuo
  8. customThe residue is purified by chromatography on a 120 g silica gel column on a Combiflash Companion™ (Isco Inc.) apparatus (gradient hexanes: TBDME from 1:0=>0:1)

出典と根拠

ORDレコード
ord-5f936b51e8e44e61910bd3c9061bb5c2
出典データセット
uspto-grants-2012_06
特許番号
US08193189B2

反応ノート

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