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

HRID 1669840노트

반응식

HRID 1669840 반응식
[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

참가 물질

5

반응물 3

HCID 27773284-(Trifluoromethoxy)phenylhydrazine hydrochlorideHCID 10942334Sodium MethoxideHCID 86604612HCID 86604612, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 887Methanol용매2회

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-b46c7ba8a09e46249c77bb4141773cac
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07989475B2

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