反应详情

To a solution of 1-(tert-butoxycarbonylamino-methyl)-spiro[2.5]octane-1-carboxylic acid methyl ester (17.9 g, 63.2 mmol) in THF (700 mL) was added HOBT (9.00 g, 66.4 mmol), 4-methylmorpholine (7.3 mL, 66.4 mmol) followed by EDC (13.9 g, 72.7 mmol). The solution was stirred for 2 hours and then concentrated ammonium hydroxide (8.5 mL, 126 mmol) was added. The mixture was stirred for 18 hours and then the solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate and half saturated potassium hydrogen sulfate. An emulsion occurred but the layers were separable. The organic layer was washed with half saturated potassium hydrogen sulfate (2 times) and brine. The organic layer was filtered to remove the emulsified solid. The organic layer was dried over sodium sulfate and filtered. Hexane was added to the filtrate to induce crystallization. The precipitate was isolated by vacuum filtration, washed with hexane and dried in a vacuum oven to give 16.2 g (91%) of (1-carbamoyl-spiro[2.5]oct-1-ylmethyl)-carbamic acid tert-butyl ester as a white solid: 1H NMR (300 MHz, CDCl3) δ 0.65 (d, J=5.0 Hz, 1H), 1.17 (d, J=5.0 Hz, 1H), 1.43(s, 9H), 1.4-1.5 (m, 4H), 1.7-1.7 (m, 6H), 3.37 (dd, J=6.0, 14.0 Hz, 1H), 3.60 (dd, J=6.0, 14.0 Hz, 1H), 5.0 (s, 1H), 5.38 (s, 1H), 6.1 (s, 1H); MS (APCI) m/z 283 [M+H]+.

1. stirringThe mixture was stirred for 18 hours
2. customthe solvent was removed under reduced pressure
3. customThe residue was partitioned between ethyl acetate and half saturated potassium hydrogen sulfate
4. washThe organic layer was washed with half saturated potassium hydrogen sulfate (2 times) and brine
5. filtrationThe organic layer was filtered
6. customto remove the emulsified solid
7. dry with materialThe organic layer was dried over sodium sulfate
8. filtrationfiltered
9. additionHexane was added to the filtrate
10. customcrystallization
11. customThe precipitate was isolated by vacuum filtration
12. washwashed with hexane
13. customdried in a vacuum oven