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 (5.0 g, 13.42 mmol) in dry DMF (75 ml) was added sodium hydride (750 mg, 33.3 mmol in 60% mineral oil) and the mixture was stirred for 30 min. Bromo-acetic acid tert-butyl ester (3.14 g, 16.11 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 (2×50 ml). The combined organic phases were dried (Na2SO4), filtered and evaporated in vacuo. The residue was dissolved in DCM (75 ml) and TFA (40 ml) was added. The resulting mixture was stirred for 16 hrs. at room temperature and evaporated in vacuo. To the residue was added water (75 ml) and diethyl ether (25 ml) and the precipitate was filtered off, washed with diethyl ether and dried in vacuo at 50° C. affording 3.3 g (74%) of [4-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]-octane-6-carbonyl)-phenylamino]-acetic acid an solid.

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 (2×50 ml)
5. dry with materialThe combined organic phases were dried (Na2SO4)
6. filtrationfiltered
7. customevaporated in vacuo
8. dissolutionThe residue was dissolved in DCM (75 ml)
9. additionTFA (40 ml) was added
10. stirringThe resulting mixture was stirred for 16 hrs
11. customat room temperature and evaporated in vacuo
12. additionTo the residue was added water (75 ml) and diethyl ether (25 ml)
13. filtrationthe precipitate was filtered off
14. washwashed with diethyl ether
15. customdried in vacuo at 50° C.