反应详情

A solution of tert-butyl benzyl(3-pent-4-enoylcyclobutyl)carbamate (7.7 g, 21.1 mmol, 5 eq), t-butyl isonitrile (12 mL, 106 mmol, 10 eq) and ammonium acetate (16.3 g, 212 mmol) in 2,2,2-trifluoroethanol (24 mL, 0.9 M) was stirred at room temperature for 3 days. The reaction mixture was diluted with ethyl acetate, quenched with 2 M HCl and extracted with ethyl acetate. The organic layer was washed successively with 2 M HCl and sat'd aq sodium chloride, dried over MgSO4, filtered and concentrated. Purification by column chromatography (ethyl acetate in hexanes) gave cis-tert-butyl 3-(2-acetamido-1-(tert-butylamino)-1-oxohex-5-en-2-yl)cyclobutyl(benzyl)carbamate as a yellow solid (8.9 g, 17.5 mmol, 83%). 1H NMR (CDCl3, 300 MHz) δ 7.32-7.10 (m, 6H), 6.08 (brs, 1H), 5.80-5.64 (m, 1H), 5.01-4.87 (m, 2H), 4.42 (brs, 2H), 4.41-4.08 (m, 1H), 2.79-2.58 (m, 1H), 2.40-1.99 (m, 8H), 1.98-1.80 (m, 3H), 1.56-1.08 (m, 18H), ESI MS found for C28H43N3O4 m/z [508.2 (M+23)] and trans-tert-butyl 3-(2-acetamido-1-(tert-butylamino)-1-oxohex-5-en-2-yl)cyclobutyl(benzyl)carbamate as a white foam (1.1 g, 2.2 mmol, 10%). 1H NMR (CDCl3, 300 MHz) δ 7.32-7.11 (m, 5H), 6.79 (brs, 1H), 5.83-5.68 (m, 1H), 5.56 (brs, 1H), 5.02-4.88 (m, 2H), 4.54-4.37 (m, 2H), 4.35-4.16 (m, 1H), 2.94-2.75 (m, 2H), 2.51-2.39 (m, 1H), 2.38-2.19 (m, 2H), 2.18-1.90 (m, 5H), 1.86-1.70 (m, 1H), 1.67-1.58 (m, 1H), 1.47-1.22 (m, 18H), ESI MS found for C28H43N3O4 m/z [486.5 (M+1), 508.0 (M+23)].

1. customquenched with 2 M HCl
2. extractionextracted with ethyl acetate
3. washThe organic layer was washed successively with 2 M HCl
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. customPurification by column chromatography (ethyl acetate in hexanes)