反应详情

温度

60 °C

A mixture of methyl (3-chloropropyl) ether (1.6 g), intermediate 4 (3.9 g), triethylamine (5 ml) and potassium iodide (a catalytic amount) in dimethylformamide (60 ml) was stirred for 48 hours at 60° C. The reaction mixture was cooled and the solvent evaporated. The residue was partitioned between CH2Cl2 and a saturated aqueous NaCl solution. The organic layer was separated, dried over MgSO4, filtered and the solvent evaporated. The residue was purified by column chromatography on silica gel (eluent: CH2Cl2 /CH3OH 90/10). The desired fractions were collected and the solvent was evaporated. The residue was solidified in DIPE, filtered off, dissolved in 2-propanol and converted into the hydrochloric acid salt (1:1) with HCl/2-propanol. The precipitate was filtered off and dried, yielding 1.14 g (22.1%) of 5-chloro-2,3-dihydro-7-[3-[1-(3-methoxypropyl)-4-piperidinyl]-1,2,4-oxadiazol-5-yl]-4-benzofuranamine monohydrochloride.hemihydrate (compound 1; mp. 244.3° C.).

1. temperatureThe reaction mixture was cooled
2. customthe solvent evaporated
3. customThe residue was partitioned between CH2Cl2
4. customThe organic layer was separated
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. customthe solvent evaporated
8. customThe residue was purified by column chromatography on silica gel (eluent: CH2Cl2 /CH3OH 90/10)
9. customThe desired fractions were collected
10. customthe solvent was evaporated
11. filtrationfiltered off
12. dissolutiondissolved in 2-propanol
13. filtrationThe precipitate was filtered off
14. customdried