反应详情

To a solution of [4-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]carbamic acid tert-butyl ester (0.5 g, 1.34 mmol) in dry DMF (40 ml) was added sodium hydride (80 mg, 3.33 mmol in 60% mineral oil) and the mixture was stirred for 30 min. 2-Chloro-1-morpholin-4-yl-ethanone (264 mg, 1.61 mmol) was added and the stirring was continued for an additional 1 hr. at 50° C. The reaction was quenched by addition of water (50 ml) and extracted with diethyl ether (2×25 ml). The combined organic phases were dried (Na2SO4), filtered and evaporated in vacuo. The residue was dissolved in DCM (20 ml) and TFA (10 ml) was added. The resulting mixture was stirred for 4 hrs. at room temperature and evaporated in vacuo. The residue was purified by column chromatography (silica gel) using first EtOAc (500 ml) followed by 4% TEA in EtOAc as eluents. Semi-pure fractions were collected and evaporated to dryness affording 0.4 g as an oil which was dissolved in EtOAc (25 ml) and washed with water (2×25 ml), dried (Na2SO4), filtered and evaporated in vacuo affording 180 mg (34%) of the title compound as a oil.

1. waitthe stirring was continued for an additional 1 hr
2. customat 50° C
3. customThe reaction was quenched by addition of water (50 ml)
4. extractionextracted with diethyl ether (2×25 ml)
5. dry with materialThe combined organic phases were dried (Na2SO4)
6. filtrationfiltered
7. customevaporated in vacuo
8. dissolutionThe residue was dissolved in DCM (20 ml)
9. additionTFA (10 ml) was added
10. stirringThe resulting mixture was stirred for 4 hrs
11. customat room temperature and evaporated in vacuo
12. customThe residue was purified by column chromatography (silica gel)
13. customSemi-pure fractions were collected
14. customevaporated to dryness
15. customaffording 0.4 g as an oil which
16. washwashed with water (2×25 ml)
17. dry with materialdried (Na2SO4)
18. filtrationfiltered
19. customevaporated in vacuo