1-Ethynylcyclohexanol → 2,2,2-trifluoro-N-(3-(3-((1-hydroxycyclohexyl)ethynyl)phenyl)propyl)acetamide

HRID 1021079

Reaction equation

HRID 1021079 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][NH:11][C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])[CH:5]=[CH:6][CH:7]=1.[C:18]([C:20]1([OH:26])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1)#[CH:19]>C(N(CC)CC)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:14][C:13]([F:16])([F:15])[C:12]([NH:11][CH2:10][CH2:9][CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:19]#[C:18][C:20]2([OH:26])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[CH:3]=1)=[O:17]

Participants

6

Reactant 2

HCID 65251-EthynylcyclohexanolHCID 57608389N-(3-(3-bromophenyl)propyl)-2,2,2-trifluoroacetamide

Product 1

HCID 866358522,2,2-trifluoro-N-(3-(3-((1-hydroxycyclohexyl)ethynyl)phenyl)propyl)acetamide

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of bromide 10 (2.0 g, 6.45 mmol) and 1-ethynylcyclohexanol (1.2 g, 9.67 mmol) in triethylamine (40 mL) was added CuI (0.0246 g, 0.129 mmol). The mixture was degassed with argon for 2-3 min, then PdCl2(PPh3)2 (0.0905 g, 0.129 mmol) was added. The reaction mixture was degassed with argon again then stirred at 70° C. overnight under argon. After cooling to room temperature, the mixture was concentrated under reduced pressure and suspended in EtOAc-hexanes (50%, 50 mL). Solids were removed by filtration and the filtrate was concentrated under reduced pressure. Purification by flash chromatography gave 2,2,2-trifluoro-N-(3-(3-((1-hydroxycyclohexyl)ethynyl)phenyl)propyl)acetamide as a clear oil. Yield (1.74 g, 76%): 1H NMR (400 MHz, DMSO-d6) δ 9.40 (br s, 1H), 7.26 (t, J=7.6 Hz, 1H), 7.17-7.24 (m, 3H), 5.37 (s, 1H), 3.16 (q, J=6.8 Hz, 2H), 2.56 (t, J=7.2 Hz, 2H), 1.15-1.83 (m, 12H).

Workup

  1. customThe mixture was degassed with argon for 2-3 min
  2. customThe reaction mixture was degassed with argon again
  3. temperatureAfter cooling to room temperature
  4. concentrationthe mixture was concentrated under reduced pressure
  5. customSolids were removed by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customPurification by flash chromatography

Sources & evidence

ORD record
ord-eb80baedcfe945518e130afc86647c47
Source dataset
uspto-grants-2014_05
Patent number
US08716529B2

Linked notes

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