tert-Butyl isocyanate → N-(3-(2-acetamido-1-(tert-butylamino)-1-oxohex-5-en-2-yl)-1-(4-chlorophenyl)cyclobutyl)benzamide

HRID 1778593Notes

Reaction equation

HRID 1778593 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([NH:18][C:19](=[O:26])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:11][CH:10]([C:12](=O)[CH2:13][CH2:14][CH:15]=[CH2:16])[CH2:9]2)=[CH:4][CH:3]=1.[C:27]([O-:30])(=O)[CH3:28].[NH4+:31].[C:32]([N:36]=[C:37]=[O:38])([CH3:35])([CH3:34])[CH3:33]>FC(F)(F)CO>[C:27]([NH:31][C:12]([CH:10]1[CH2:11][C:8]([NH:18][C:19](=[O:26])[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[CH2:9]1)([CH2:13][CH2:14][CH:15]=[CH2:16])[C:37]([NH:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:38])(=[O:30])[CH3:28]

Participants

5

Reactant 3

HCID 62412tert-Butyl isocyanateHCID 517165Ammonium AcetateHCID 89514447N-(1-(4-chlorophenyl)-3-pent-4-enoylcyclobutyl)benzamide

Product 1

HCID 89514269N-(3-(2-acetamido-1-(tert-butylamino)-1-oxohex-5-en-2-yl)-1-(4-chlorophenyl)cyclobutyl)benzamide

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

Procedure

A suspension of N-(1-(4-chlorophenyl)-3-pent-4-enoylcyclobutyl)benzamide (1.21 g, 3.0 mmol), ammonium acetate (2.08 g, 27.0 mmol) in 2,2,2-trifluoroethanol (12 mL) was treated with tert-butylisocyanate (2 mL, 18.0 mmol). After stirring for three days at room temperature, the reaction was quenched with 1M HCl (5 mL) and diluted with ethyl acetate (15 mL). After vigorous stirring for 1 h, the phases were separated and the organic layer was washed successively with 1 M HCl, water and saturated aqueous sodium chloride. The solution was dried over MgSO4, filtered and concentrated to give the crude product as a mixture of diastereomers (1.77 g). It was used to the next step without further purification. ESI MS found for C29H36ClN3O3 m/z [510.7/512.7 (M+1), 508.7/509.9 (M−1)].

Workup

  1. customthe reaction was quenched with 1M HCl (5 mL)
  2. additiondiluted with ethyl acetate (15 mL)
  3. stirringAfter vigorous stirring for 1 h
  4. customthe phases were separated
  5. washthe organic layer was washed successively with 1 M HCl, water and saturated aqueous sodium chloride
  6. dry with materialThe solution was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-9cffcd0f96714d80a63fb2003992f11b
Source dataset
uspto-grants-2016_02
Patent number
US09266908B2

Reaction notes

Loading…