反应详情

To a solution of CBz-D-phenylglycine (877 mg, 3.1 mmol) in anhydrous THF (40 ml) at −25° C. was added N-methylmorpholine (336 μl, 3.1 mmol) and isobutyl chloroformate (419 μl, 3.1 mmol). The resulting suspension was left to stir for 5 min at this temperature and then the t-Butyl 4-(piperidin-4-yl)piperidine-1-carboxylate (825 mg, 3.1 mmol) in anhydrous THF (5 ml) was added in one portion at −25° C. and the reaction mixture allowed to warm to room temperature over 1 hour. The N-methylmorpholine hydrochloride was filtered off and the THF removed under vacuo. The resulting solid was treated with TFA/DCM (20 ml, 1:1) and the reaction mixture left to stir for 2 hours. The organics were removed under vacuo, the residue dissolved in ethyl acetate (100 ml), washed with aq. sodium bicarbonate solution, brine, dried and concentrated to yield the title compound as a clear oil (1.12 g, 84% over two steps).

1. waitThe resulting suspension was left
2. filtrationThe N-methylmorpholine hydrochloride was filtered off
3. customthe THF removed under vacuo
4. additionThe resulting solid was treated with TFA/DCM (20 ml, 1:1)
5. waitthe reaction mixture left
6. stirringto stir for 2 hours
7. customThe organics were removed under vacuo
8. dissolutionthe residue dissolved in ethyl acetate (100 ml)
9. washwashed with aq. sodium bicarbonate solution, brine
10. customdried
11. concentrationconcentrated