1-Vinylcyclohexyl alcohol → (E)-2,2,2-trifluoro-N-(3-(3-fluoro-5-(2-(1-hydroxycyclohexyl)vinyl)phenyl)-3-hydroxypropyl)acetamide

HRID 1021134ノート

反応式

HRID 1021134 の反応式
Br[C:2]1[CH:3]=[C:4]([CH:9]([OH:19])[CH2:10][CH2:11][NH:12][C:13](=[O:18])[C:14]([F:17])([F:16])[F:15])[CH:5]=[C:6]([F:8])[CH:7]=1.[CH:20]([C:22]1([OH:28])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1)=[CH2:21]>C([O-])(=O)C.C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:15][C:14]([F:17])([F:16])[C:13]([NH:12][CH2:11][CH2:10][CH:9]([C:4]1[CH:3]=[C:2](/[CH:21]=[CH:20]/[C:22]2([OH:28])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[CH:7]=[C:6]([F:8])[CH:5]=1)[OH:19])=[O:18]

参加物

6

反応物 2

HCID 747411-Vinylcyclohexyl alcoholHCID 86635868N-(3-(3-bromo-5-fluorophenyl)-3-hydroxypropyl)-2,2,2-trifluoroacetamide

生成物 1

HCID 86635867(E)-2,2,2-trifluoro-N-(3-(3-fluoro-5-(2-(1-hydroxycyclohexyl)vinyl)phenyl)-3-hydroxypropyl)acetamide

試薬・触媒・溶媒 3

HCID 82707Tetrabutylammonium Acetate触媒HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

A mixture of N-(3-(3-bromo-5-fluorophenyl)-3-hydroxypropyl)-2,2,2-trifluoroacetamide (0.58 g, 1.57 mmol), 1-vinylcyclohexanol (0.3 g, 2.38 mmol) and palladium acetate (0.03 g, 0.12 mmol) in tetrabutyl ammonium acetate (1.0 g) and DMF (1 ml) was heated at 90° C. for 1 h. After cooled to room temperature, the reaction mixture was partitioned between water (40 ml) and ethyl acetate (60 ml). Ethyl acetate portion was dried over Na2SO4. Purification by chromatography (40 to 60% EtOAc-hexanes gradient) gave (E)-2,2,2-trifluoro-N-(3-(3-fluoro-5-(2-(1-hydroxycyclohexyl)vinyl)phenyl)-3-hydroxypropyl)acetamide as a colorless oil. Yield (0.25 g, 54%): H NMR (400 MHz, DMSO-d6) δ 9.32 (t, J=5.6 Hz, 1H), 6.94-7.18 (m, 3H), 6.41-6.53 (m, 2H), 5.42 (d, J=4.4 Hz, 1H), 4.54-4.60 (m, 1H), 3.18-3.26 (m, 2H), 1.72-1.86 (m, 2H), 1.38-1.66 (m, 10H).

後処理

  1. temperatureAfter cooled to room temperature
  2. customthe reaction mixture was partitioned between water (40 ml) and ethyl acetate (60 ml)
  3. dry with materialEthyl acetate portion was dried over Na2SO4
  4. customPurification by chromatography (40 to 60% EtOAc-hexanes gradient)

出典と根拠

ORDレコード
ord-dbfdb9eb5dc04155afd8d7939da08e97
出典データセット
uspto-grants-2014_05
特許番号
US08716529B2

反応ノート

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