Water → HCID 178446404, compound

HRID 579590Notes

Reaction equation

HRID 579590 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]([C:14]2([C@@H:19]3[CH2:24][CH2:23][C@H:22]([C:25](=O)[CH2:26][CH2:27][CH:28]=[CH2:29])[CH2:21][CH2:20]3)[O:18][CH2:17][CH2:16][O:15]2)=[CH:10][CH:9]=1.[C:31]([O-:34])(=O)[CH3:32].[NH4+:35].[OH2:36]>FC(F)(F)CO>[C:1]([NH:5][C:6](=[O:36])[C:25]([NH:35][C:31](=[O:34])[CH3:32])([C@H:22]1[CH2:21][CH2:20][C@@H:19]([C:14]2([C:11]3[CH:12]=[CH:13][C:8]([Cl:7])=[CH:9][CH:10]=3)[O:18][CH2:17][CH2:16][O:15]2)[CH2:24][CH2:23]1)[CH2:26][CH2:27][CH:28]=[CH2:29])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 23577Tert-Butyl isocyanideHCID 517165Ammonium AcetateHCID 178447107HCID 178447107, compound

Product 1

HCID 178446404HCID 178446404, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

Procedure

tert-Butyl isocyanide (404 mg, 0.55 mL, 4.86 mmol) was added to a stirred slurry of cis-1-{4-[2-(4-chlorophenyl)-[1,3]-dioxolan-2-yl]-cyclohexyl}pent-4-en-1-one (1.13 g, 3.24 mmol) and ammonium acetate (999 mg, 12.96 mmol) in 2,2,2-trifluoroethanol (0.5 mL), and the resultant slurry was stirred at room temperature. After 8 days the reaction 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 cis-2-acetylamino-2-{4-[2-(4-chlorophenyl)-[1,3]-dioxolan-2-yl]-cyclohexyl}hex-5-enoic acid, tert-butylamide as a colorless oil (1.16 g, 71%); 1H NMR (CDCl3, 300 MHz) δ 7.29 (m, 4H), 6.96 (br s, 1H NH), 5.76 (m, 1H), 5.44 (br s, NH, 1H), 4.94 (m, 2H), 3.94 (m, 2H), 3.68 (m, 2H), 2.93 (ddd, J1=16.5 hz, J2=11.5 Hz, J3=5.0 Hz, 1H), 1.90-2.08 (m, 2H), 1.96 (s, 3H), 1.60-1.86 (m, (6H), 1.42 (m, 1H), 1.34 (s, 9H), 1.06 (m, 3H) and 0.86 (m, 1H).

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-7eba051b279b40ceb4f25e162383be32
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

Loading…