反应详情

The procedure of Example 2 is followed, but starting with the A isomer of 4-(2-bromoethyl)-3,4-dihydro-(2H)-benzopyran (1.5 g) and 4-(3,4-dimethoxyphenyl)piperidine hydrochloride (1.78 g), followed by dry potassium carbonate (1.71 g) and by potassium iodide (1.03 g) in 2-butanone (50 cc). The oil obtained is taken up with ethyl acetate (50 cc). The organic phase is washed with a 1N solution of sodium hydroxide (10 cc) and then with water and is then dried over magnesium sulphate. It is then concentrated to dryness under reduced pressure and the residue is chromatographed on a column 3 cm in diameter, containing silica gel (25 g), using a dichloromethane-acetone mixture (70-30 by volume) as eluent and collecting 100-cc fractions. The first five fractions are concentrated to dryness. The oil obtained is dissolved while hot in the minimum quantity of isopropyl alcohol and then this solution is added to a warm solution of fumaric acid (0.696 g) in isopropyl alcohol. After return to a temperature in the region of 20° C., the crystals formed are filtered off and then recrystallized from isopropanol (100 cc). The A isomer of 1-[2-(3,4-dihydro-1(2H)-benzopyran-4-yl)ethyl]-4-(3,4-dimethoxyphenyl)piperidine fumarate (2.4 g) is thus obtained in the form of a white solid melting at 170° C.

1. customThe oil obtained
2. washThe organic phase is washed with a 1N solution of sodium hydroxide (10 cc)
3. dry with materialwith water and is then dried over magnesium sulphate
4. concentrationIt is then concentrated to dryness under reduced pressure
5. customthe residue is chromatographed on a column 3 cm in diameter
6. additioncontaining silica gel (25 g)
7. customcollecting 100-cc fractions
8. concentrationThe first five fractions are concentrated to dryness
9. customThe oil obtained
10. customAfter return to a temperature in the region of 20° C., the crystals formed
11. filtrationare filtered off
12. customrecrystallized from isopropanol (100 cc)