2,2,2-Trifluoroethanol → 2-acetamido-N-tert-butyl-2-(3-(4-chlorobenzyl)-3-formamidocyclobutyl)hex-5-enamide

HRID 1778599Notes

Reaction equation

HRID 1778599 reaction equation
[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][C:7]2([NH:17][CH:18]=[O:19])[CH2:10][CH:9]([C:11](=O)[CH2:12][CH2:13][CH:14]=[CH2:15])[CH2:8]2)=[CH:4][CH:3]=1.[C:22]([O-:25])(=O)[CH3:23].[NH4+:26].[C:27]([N+:31]#[C-])([CH3:30])([CH3:29])[CH3:28].FC(F)(F)[CH2:35][OH:36]>C(OCC)(=O)C>[C:22]([NH:26][C:11]([CH:9]1[CH2:10][C:7]([CH2:6][C:5]2[CH:20]=[CH:21][C:2]([Cl:1])=[CH:3][CH:4]=2)([NH:17][CH:18]=[O:19])[CH2:8]1)([CH2:12][CH2:13][CH:14]=[CH2:15])[C:35]([NH:31][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:36])(=[O:25])[CH3:23]

Participants

6

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 23577Tert-Butyl isocyanideHCID 517165Ammonium AcetateHCID 89514331N-(1-(4-chlorobenzyl)-3-pent-4-enoylcyclobutyl)formamide

Product 1

HCID 895143752-acetamido-N-tert-butyl-2-(3-(4-chlorobenzyl)-3-formamidocyclobutyl)hex-5-enamideYield 45%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of N-(1-(4-chlorobenzyl)-3-pent-4-enoylcyclobutyl)formamide (0.5 g, 1.64 mmol) and ammonium acetate (1.14 g, 9.84 mmol) in 2,2,2-trifluoroethanol (4 mL). was treated with tert-butyl isocyanide (1.1 mL, 9.84 mmol) and stirred at room temperature for 3 days. Once complete, the solution was diluted with ethyl acetate (15 mL) and quenched with 2M HCl (10 mL). After stirring vigorously for 1 h, the phases were separated and the organic layer was washed with water and saturated aqueous sodium chloride, dried over MgSO4, filtered and concentrated. Purification by column chromatography (gradient 25-75% ethyl acetate in heptane) afforded the subject compound as a colorless oil (330, mg, 45% yield). ESI MS found for C24H34ClN3O3 m/z [448.6 (M+1), 470.6 (M+Na+), 446.3 (M−1)].

Workup

  1. customquenched with 2M HCl (10 mL)
  2. stirringAfter stirring vigorously for 1 h
  3. customthe phases were separated
  4. washthe organic layer was washed with water and saturated aqueous sodium chloride
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by column chromatography (gradient 25-75% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-c65f2e37aeba4e3895a218afa919948a
Source dataset
uspto-grants-2016_02
Patent number
US09266908B2

Reaction notes

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