反应详情

A mixture of benzyl (3-bromopropyl)aminoformate (495.2 g, 1.82 mol), prepared as in Example 6, 1-(2-methoxyphenyl)piperazine hydrochloride (377.9 g, 1.65 mol) and potassium carbonate (456.8 g, 3.31 mol) in 3L of DMF was stirred at 80° to 81° C. for 3.5 hours. The mixture was allowed to cool to room temperature and then poured into 20L of water. The mixture was extracted with ethyl acetate (3×4L). The combined ethyl acetate extracts were washed with water (2×1L) and saturated aqueous sodium chloride (1×1L), dried (Na2SO4) and treated with silica gel (200 g). The ethyl acetate was filtered and 11L of the filtrate was added slowly to 200 mL of 5.5N hydrochloric acid (2.75 mol) in ethanol at a rate such that the reaction temperature did not exceed 23° C. The mixture was aged at room temperature for 1 hour and filtered. The filtered residue was washed with ethyl acetate (3×500 mL), dried under a stream of air for 17 hours and then dried under reduced pressure at 60° C. to give benzyl 3-[4-(2-methoxyphenyl)piperazin-1-yl]propylaminoformate dihydrochloride (496 g, 1.09 mol), m.p. 174°-176° C.

1. extractionThe mixture was extracted with ethyl acetate (3×4L)
2. washThe combined ethyl acetate extracts were washed with water (2×1L) and saturated aqueous sodium chloride (1×1L)
3. dry with materialdried (Na2SO4)
4. additiontreated with silica gel (200 g)
5. filtrationThe ethyl acetate was filtered
6. customdid not exceed 23° C
7. waitThe mixture was aged at room temperature for 1 hour
8. filtrationfiltered
9. washThe filtered residue was washed with ethyl acetate (3×500 mL)
10. customdried under a stream of air for 17 hours
11. customdried under reduced pressure at 60° C.