Water → 2-acetamido-N-tert-butyl-2-(4-(4-chlorophenyl)cyclohexyl)hex-5-enamide

HRID 579598Notes

Reaction equation

HRID 579598 reaction equation
[C:1]([N+:5]#[C-:6])([CH3:4])([CH3:3])[CH3:2].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]2[CH2:19][CH2:18][CH:17]([C:20](=O)[CH2:21][CH2:22][CH:23]=[CH2:24])[CH2:16][CH2:15]2)=[CH:10][CH:9]=1.[C:26]([O-:29])(=O)[CH3:27].[NH4+:30].[OH2:31]>FC(F)(F)CO>[C:26]([NH:30][C:20]([CH:17]1[CH2:18][CH2:19][CH:14]([C:11]2[CH:12]=[CH:13][C:8]([Cl:7])=[CH:9][CH:10]=2)[CH2:15][CH2:16]1)([CH2:21][CH2:22][CH:23]=[CH2:24])[C:6]([NH:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:31])(=[O:29])[CH3:27]

Participants

6

Reactant 4

HCID 962WaterHCID 23577Tert-Butyl isocyanideHCID 517165Ammonium AcetateHCID 668327641-[4-(4-Chlorophenyl)-cyclohexyl]pent-4-en-1-one

Product 1

HCID 668336582-acetamido-N-tert-butyl-2-(4-(4-chlorophenyl)cyclohexyl)hex-5-enamideYield 77%

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

Procedure

tert-Butyl isocyanide (301 mg, 0.41 mL, 3.6 mmol) was added to a stirred slurry of 1-[4-(4-chlorophenyl)-cyclohexyl]pent-4-en-1-one (800 mg, 2.9 mmol) and ammonium acetate (671 mg, 8.7 mmol) in 2,2,2-trifluoroethanol (0.4 mL). After stirring at room temperature for 8 days, the reaction mixture was poured into water and extracted with ethyl acetate (3×). The combined organic phase was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography (silica gel, 10-50% ethyl acetate in heptane) gave 2-acetamido-N-tert-butyl-2-(4-(4-chlorophenyl)cyclohexyl)hex-5-enamide as a colorless oil (940 mg, 77%); 1H NMR (CDCl3, 300 MHz) δ 7.24 (m, 2H), 7.15 (m, 2H), 7.04 (br s, NH, 1H), 5.80 (m, 1H), 5.544 (br s, NH, 1H), 4.97 (m, 2H), 3.04 (ddd, J1=14 Hz, J2=11.5 Hz, J3=5.0 Hz, 1H), 2.38 (tt, J1=12 Hz, J2=2 Hz, 1H), 2.28 (tt, J1=12 Hz, J2=2 Hz, 1H), 2.03 (s, 3H), 1.68-1.95 (m, 5H), 1.42-1.61 (m, 4H), 1.41 (s, 9H), 1.26 (m, 1H) and 1.12 (m, 1H); MS (+CI): m/z for C24H35ClN2O2: expected 418.2. found 419.2 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. washThe combined organic phase was washed with saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash column chromatography (silica gel, 10-50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-c155a9d4a2f54fc7b4545d6b462b08ee
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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