反应详情

To a stirring solution of triphosgene (2.7 g, 9.0 mmol) in dichloromethane (100 mL) was added, dropwise via an addition funnel, a solution of 2-bromo-4-chloroaniline (5 g, 24.2 mmol) and N,N-diisopropylethylamine (6.9 g, 53.2 mmol) in dichloromethane (50 mL). After complete addition and an additional hour, a solution of N-Boc-piperazine (5 g, 26.6 mmol) in dichloromethane (50 mL) was added. After stirring overnight, the solvent was removed in vacuo and the residue was partitioned between ethyl acetate and water. The organic phase was separated and washed consecutively with 1 M citric acid, brine, sat. aq sodium bicarbonate and finally with brine, then dried with MgSO4, filtered and concentrated in vacuo. The residue was then dissolved in a minimal amount of chloroform and chromatographed over silica gel, eluting with 20% ethyl acetate in hexanes followed by 30% ethyl acetate in hexanes. The product containing fractions were combined and concentrated in vacuo and the resulting solid was suspended in diethyl ether, sonicated and then filtered and dried in vacuo to give 7.2 g (71%) of a white powder.

1. additionAfter complete addition
2. customthe solvent was removed in vacuo
3. customthe residue was partitioned between ethyl acetate and water
4. customThe organic phase was separated
5. washwashed consecutively with 1 M citric acid, brine, sat. aq sodium bicarbonate and finally with brine
6. dry with materialdried with MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. dissolutionThe residue was then dissolved in a minimal amount of chloroform
10. customchromatographed over silica gel
11. washeluting with 20% ethyl acetate in hexanes
12. additionThe product containing fractions
13. concentrationconcentrated in vacuo
14. customsonicated
15. filtrationfiltered
16. customdried in vacuo