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

HRID 658874

반응식

HRID 658874 반응식
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]

참가 물질

6

반응물 2

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

생성물 1

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

시약·촉매·용매 3

HCID 82707Tetrabutylammonium Acetate촉매HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매

반응 조건

온도
90 °C

실험 절차

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%): 1H 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).

후처리

  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)

출처 및 근거

ORD 기록
ord-70141492a82e4c45bd57d41fd6cd9843
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08076516B2

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