Hydrochloric Acid → tert-butyl 4-(tert-butylcarbamoyl)-4-(N-methylacetamido)oct-7-enylcarbamate

HRID 579540Notes

Reaction equation

HRID 579540 reaction equation
O=[C:2]([CH2:14][CH2:15][CH:16]=[CH2:17])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10].[C:18]([O-:21])(=O)[CH3:19].[CH3:22][NH3+:23].[C:24]([N+:28]#[C-])([CH3:27])([CH3:26])[CH3:25].Cl.FC(F)(F)[CH2:33][OH:34]>C(OCC)(=O)C>[C:24]([NH:28][C:33]([C:2]([N:23]([CH3:22])[C:18](=[O:21])[CH3:19])([CH2:14][CH2:15][CH:16]=[CH2:17])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:34])([CH3:25])([CH3:26])[CH3:27]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 64092,2,2-TrifluoroethanolHCID 23577Tert-Butyl isocyanideHCID 11564973Tert-butyl 4-oxooct-7-enylcarbamateHCID 14420923Methylammoniumacetat

Product 1

HCID 86663727tert-butyl 4-(tert-butylcarbamoyl)-4-(N-methylacetamido)oct-7-enylcarbamateYield 26%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of tert-butyl 4-oxooct-7-enylcarbamate (300 mg; 1.24 mmol), methylammonium acetate (680 mg, 7.46 mmol) in 2,2,2-trifluoroethanol (2 mL) was treated with tert-butyl isocyanide (0.56 mL, 5.0 mmol) and stirred at room temperature for 5 days. Ethyl acetate (5 mL) and 2 M aq HCl (2 mL) were added and the solution was vigorously stirred for 3 additional hrs. The phases were separated and the organic phase was washed successively with water and sat'd aq sodium chloride, dried over MgSO4, filtered and concentrated. The crude viscous yellow oil residue was purified by flash column chromatography (2% methanol in dichloromethane) to give tert-butyl 4-(tert-butylcarbamoyl)-4-(N-methylacetamido)oct-7-enylcarbamate (130 mg, 26%). 1H NMR (CDCl3, 500 MHz) δ 5.81-5.73 (m, 1H), 5.40 (s, 1H), 5.05-4.96 (m, 2H), 4.62 (bs, 1H), 3.15-3.09 (m, 2H), 3.01 (s, 3H) 2.17-2.12 (m, 2H), 2.10 (s, 3H) 2.04-1.94 (m, 2H), 1.77-1.71 (m, 2H), 1.43 (s, 9H), 1.38-1.34 (m, 2H), 1.32 (s, 9H). ESI MS found for C21H39N3O4 m/z [420.5 (M+Na+), 442.4 (M+HCOO−), 396.6 (M−1)].

Workup

  1. stirringthe solution was vigorously stirred for 3 additional hrs
  2. customThe phases were separated
  3. washthe organic phase was washed successively with water
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude viscous yellow oil residue was purified by flash column chromatography (2% methanol in dichloromethane)

Sources & evidence

ORD record
ord-a0e5572f1c124714b9d674d90a094608
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

Loading…