3-Ethyl-1-pentyn-3-ol → N-(3-(3-(3-ethyl-3-hydroxypentyl)phenyl)propyl)-2,2,2-trifluoroacetamide

HRID 517106Notes

Reaction equation

HRID 517106 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.[CH2:18]([C:20]([OH:25])([CH2:23][CH3:24])[C:21]#[CH:22])[CH3:19].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(N(CC)CC)C.CN(C=O)C.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.[Cu]I>[CH2:18]([C:20]([OH:25])([CH2:23][CH3:24])[CH2:21][CH2:22][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)[CH3:19]

Participants

8

Reactant 3

HCID 226983-Ethyl-1-pentyn-3-olHCID 80271Tri-o-tolylphosphineHCID 57608389N-(3-(3-bromophenyl)propyl)-2,2,2-trifluoroacetamide

Product 1

HCID 86628449N-(3-(3-(3-ethyl-3-hydroxypentyl)phenyl)propyl)-2,2,2-trifluoroacetamide

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
90 °C

Procedure

To a degassed solution of N-(3-(3-bromophenyl)propyl)-2,2,2-trifluoroacetamide (3) (0.930 g, 3 mmol) and 3-ethylpent-1-yn-3-ol (4) (0.670 g, 6 mmol) in triethylamine (4 mL) and DMF (12 mL) was added PdCl2(PPh3)2 (0.053 g, 0.075 mmol), tri-o-tolylphosphine (0.046 g, 0.15 mmol), and CuI (0.014 g, 0.075 mmol). The resulting mixture was degassed and stirred under argon at 90° C. for 6 h. The mixture was cooled to room temperature then concentrated under reduced pressure and diluted with EtOAc (100 mL) and water (70 mL). After vigorous shaking, the layers were separated. The organic layer was treated with charcoal, dried over MgSO4, filtered, and concentrated under reduced pressure. Purification by flash column chromatography (7 to 60% EtOAc-hexanes gradient) gave N-(3-(3-(3-ethyl-3-hydroxypentyl)phenyl)propyl)-2,2,2-trifluoroacetamide (5) as a yellow oil. Yield (0.663 g, 65%): 1H NMR (400 MHz, DMSO-d6) δ 9.40 (s, 1H), 7.17-7.28 (m, 4H), 5.11 (s, 1H), 3.16 (q, J=7.2 Hz, 2H), 2.56 (t, J=7.2 Hz, 2H), 1.76 (quint, J=7.2 Hz, 2H), 1.53-1.67 (m, 4H), 0.97 (t, J=7.2 Hz, 6H).

Workup

  1. customThe resulting mixture was degassed
  2. temperatureThe mixture was cooled to room temperature
  3. concentrationthen concentrated under reduced pressure
  4. additiondiluted with EtOAc (100 mL) and water (70 mL)
  5. customAfter vigorous shaking, the layers were separated
  6. additionThe organic layer was treated with charcoal
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash column chromatography (7 to 60% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-1bd861e7e5894262895f7b027a504050
Source dataset
uspto-grants-2015_08
Patent number
US09115056B2

Reaction notes

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