反应详情

To a solution of 240 mg (0.51 mmol) of (1-benzylcyclobutyl)methyl(1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate in 2 mL of dichloromethane at 0° C. was added 1 mg of 2,2,6,6-tetramethyl-1-piperidinyloxy free radical and 5 mg of potassium bromide. A solution of 30 mg of sodium bicarbonate in 2.5 mL of household bleach was added and the reaction stirred for 30 min. The reaction was extracted with ethyl acetate and and washed 0.5 N hydrochloric acid. The organic phase was washed with saturated sodium bicarbonate, washed with brine, dried over magnesium sulfate, and concentrated under vacuum. The product was purified by silica chromatography eluting with 2.5:7.5 acetone:hexanes to afford 128 mg (53%) of (1-benzylcyclobutyl)methyl(1S)-1-(oxo{[(1R)-1-phenylethyl]amino}acetyl)pentylcarbamate. M.P.=96-98° C. Elemental analysis: Theory; C=72.39%, H=7.81%, N=6.03%. Found; C=72.14%, H=7.81%, N=5.99%. 1H NMR (300 MHz, 80° C., DMSO-d6) δ 8.83 (d, J=8 Hz, 1H), 7.19-7.38 (m, 11H), 5.02 (qnt, J=7 Hz, 1H), 4.85 (m, 1H), 3.83 (s, 2H), 2.79 (s, 1H), 1.67-1.89 (m, 7H), 1.51-1.60 (m, 1H), 1.47 (d, J=7 Hz, 3H), 1.25-1.40 (m, 4H), 0.86 (t, J=7 Hz, 3H). ES-LCMS m/z 487 (M+Na). HRMS C28H36N2O4 m/z 487.2573 (M+Na)Cal; 487.2552 (M+Na)Obs.

1. extractionThe reaction was extracted with ethyl acetate
2. washwashed 0.5 N hydrochloric acid
3. washThe organic phase was washed with saturated sodium bicarbonate
4. washwashed with brine
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated under vacuum
7. customThe product was purified by silica chromatography
8. washeluting with 2.5:7.5 acetone