4-(Trifluoromethoxy)phenylhydrazine hydrochloride → 4-[(4-Bromophenyl)methyl]-5-cyclohexyl-1-[4-(trifluoromethoxy)phenyl]-1H-pyrazole

HRID 2102227ノート

反応式

HRID 2102227 の反応式
[Br:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][CH:7]([C:10]([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)=O)[CH:8]=O)=[CH:4][CH:3]=1.Cl.[F:21][C:22]([F:33])([F:32])[O:23][C:24]1[CH:29]=[CH:28][C:27]([NH:30][NH2:31])=[CH:26][CH:25]=1.C[O-].[Na+]>CO>[Br:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][C:7]2[CH:8]=[N:31][N:30]([C:27]3[CH:28]=[CH:29][C:24]([O:23][C:22]([F:21])([F:33])[F:32])=[CH:25][CH:26]=3)[C:10]=2[CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 27773284-(Trifluoromethoxy)phenylhydrazine hydrochlorideHCID 10942334Sodium MethoxideHCID 86604612HCID 86604612、化合物

生成物 1

HCID 673347364-[(4-Bromophenyl)methyl]-5-cyclohexyl-1-[4-(trifluoromethoxy)phenyl]-1H-pyrazole

試薬・触媒・溶媒 1

HCID 887Methanol溶媒2 回

実験手順

To a solution of 3.17 g 2-(4-bromobenzyl)-3-cyclohexyl-3-oxopropanal from Step C above and 2.47 g 4-trifluoromethoxyphenylhydrazine hydrochloride in 100 mL methanol was added 21.6 mL 0.5 M sodium methoxide in methanol. The resulting mixture was refluxed under nitrogen for two days. The solvent was removed under reduced pressure. The resulting crude product was subjected to repeated chromatography on silica gel using 0˜10% MeCN in methylene chloride, 0˜2% MeCN in methylene chloride, or 7˜10% EtOAc in hexanes. Pure 4-(4-bromobenzyl)-5-cyclohexyl-1-[4-(trifluoromethoxy)phenyl]-1H-pyrazole was obtained as the major product by recrystallization of chromatographic fractions from methanol. 1H NMR (CDCl3, 500 MHz) δ 7.64˜7.67 (m, 2H), 7.43˜7.46 (m, 2H), 7.44 (s, 1H), 7.23˜7.27 (m, 2H), 7.10˜7.13 (m, 2H), 3.82 (s, 2H), 2.63 (tt, J=3.3 & 11.8 Hz, 1H), 1.83˜1.89 (m, 4H), 1.72˜1.76 (m, 1H), 1.60˜1.69 (m, 2H), 1.27˜1.40 (m, 3H). LC-MS: 2.91 min. (M+H=479). Pure 4-(4-bromobenzyl)-3-cyclohexyl-1-[4-(trifluoromethoxy)phenyl]-1H-pyrazole was obtained as the minor product following preparative HPLC of the silica gel chromatography fractions. 1H NMR (CDCl3, 500 MHz) δ 7.59˜7.63 (m, 2H), 7.44˜7.47 (m, 2H), 7.41 (s, 1H), 7.25˜7.28 (m, 2H), 7.10˜7.13 (m, 2H), 3.82 (s, 2H), 2.64 (tt, J=3.2 & 12.1 Hz, 1H), 1.83˜1.89 (m, 4H), 1.72˜1.76 (m, 1H), 1.57˜1.66 (m, 2H), 1.27˜1.39 (m, 3H). LC-MS: 2.70 min. (M+H=479.1/481). The identity of the isomers were confirmed by NOE difference spectra.

後処理

  1. temperatureThe resulting mixture was refluxed under nitrogen for two days
  2. customThe solvent was removed under reduced pressure

出典と根拠

ORDレコード
ord-c660e4673ced48e2a3bbb99748931a6a
出典データセット
uspto-grants-2009_08
特許番号
US07572922B2

反応ノート

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