反应详情

To a solution of (5-cyclohexyl-2-oxo-1,2-dihydro-benzo[e][1,2,4]triazepin-3-yl)-acetic acid ethyl ester (50 g, 151.7 mmol) in DMF (250 mL) was added potassium carbonate (325 mesh, 102 g, 738 mmol) and tetrabutylammonium iodide (46.0 g, 124.5 mmol). The resulting mixture was heated to about 50-55° C. and while at this temperature, 2-chloro-1-cyclopentylethanone (57.0 g, 373.5 mmol) was added drop-wise over a period of about 1 hr. The reaction mixture was then aged for 1 hr, cooled to ambient temperature and diluted with MTBE (50 mL). The inorganic solids were removed by filtration and rinsed with additional MTBE (50 mL). To the combined filtrates was added DMF (50 mL) and the resulting mixture was treated with 3N NaOH (150 mL), then stirred at −30° C. for about 1 hr. The reaction mixture was then again diluted with MTBE (100 mL) and the layers were separated. The aqueous layer was poured slowly under vigorous agitation, into another flask containing cold 2N HCl solution (400 mL) which was maintained at ˜5° C. Isopropyl acetate (300 mL) was added to the reaction mixture and the layers were separated. The organic layer was rinsed with water (300 mL) and then diluted with n-heptane (300 mL), at which point a solid was observed to precipitate. The precipitate was filtered and dried under vacuum to constant weight to yield the title compound as an off-white solid.

1. additionwas added drop-wise over a period of about 1 hr
2. customThe inorganic solids were removed by filtration
3. washrinsed with additional MTBE (50 mL)
4. additionTo the combined filtrates was added DMF (50 mL)
5. additionthe resulting mixture was treated with 3N NaOH (150 mL)
6. additionThe reaction mixture was then again diluted with MTBE (100 mL)
7. customthe layers were separated
8. additionThe aqueous layer was poured slowly under vigorous agitation, into another flask
9. additioncontaining cold 2N HCl solution (400 mL) which
10. temperaturewas maintained at ˜5° C
11. additionIsopropyl acetate (300 mL) was added to the reaction mixture
12. customthe layers were separated
13. washThe organic layer was rinsed with water (300 mL)
14. additiondiluted with n-heptane (300 mL), at which point a solid
15. customto precipitate
16. filtrationThe precipitate was filtered
17. customdried under vacuum to constant weight