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

HRID 658874

Reaction equation

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]

Participants

Conditions

Temperature: 90 °C

Procedure

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).

Workup

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

Sources & evidence

ORD record: ord-70141492a82e4c45bd57d41fd6cd9843
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08076516B2

Linked notes

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