Hydrochloric Acid → Tert-butyl 4-acetamido-4-(tert-butylcarbamoyl)oct-7-enylcarbamate

HRID 579551Notes

Reaction equation

HRID 579551 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].[NH4+:22].[C:23]([N+:27]#[C-])([CH3:26])([CH3:25])[CH3:24].Cl.FC(F)(F)[CH2:32][OH:33]>C(OCC)(=O)C>[C:18]([NH:22][C:2]([C:32](=[O:33])[NH:27][C:23]([CH3:26])([CH3:25])[CH3:24])([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:21])[CH3:19]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 64092,2,2-TrifluoroethanolHCID 23577Tert-Butyl isocyanideHCID 517165Ammonium AcetateHCID 11564973Tert-butyl 4-oxooct-7-enylcarbamate

Product 1

HCID 86663730Tert-butyl 4-acetamido-4-(tert-butylcarbamoyl)oct-7-enylcarbamateYield 66%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of tert-butyl 4-oxooct-7-enylcarbamate (Example 159, 2.17 g, 8.99 mmol) and ammonium acetate (4.16 g, 53.9 mmol) in 2,2,2-trifluoroethanol (7 mL) was treated with tert-butyl isocyanide (4.1 mL, 35.9 mmol) and stirred at room temperature for 3 days. Ethyl acetate (15 mL) and 2 M aq HCl (10 mL) were added and the solution was vigorously stirred for an additional 3 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 residue was purified by flash column chromatography (5-50% ethyl acetate in hexanes) to give tert-butyl 4-acetamido-4-(tert-butylcarbamoyl)oct-7-enylcarbamate (2.27 g, 66%). 1H NMR (CDCl3, 500 MHz) δ 6.97 (s, 1H), 5.79-5.70 (m, 1H), 5.56 (s, 1H), 4.99-4.92 (m, 2H), 4.55 (bs, 1H), 3.08-3.06 (m, 2H), 2.78-2.67 (m, 2H), 2.03-1.93 (m, 1H), 1.99 (s, 3H), 1.84-1.76 (m, 1H), 1.42 (s, 9H), 1.38-1.34 (m, 2H), 1.36 (s, 9H), 1.29-1.24 (m, 2H), ESI MS found for C20H37N3O4 m/z [406.5 (M+Na+), 384.6 (M+1), 382.5 (M−1)].

Workup

  1. stirringthe solution was vigorously stirred for an additional 3 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 residue was purified by flash column chromatography (5-50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-1fbf6ad20ac04546bb1823e6ab1789da
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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