反应详情

温度

-50 °C

A solution of boron tribromide (5.01 g) in methylene chloride (100 cc) is added dropwise and with stirring during 15 minutes to a solution, cooled to -50° C., of N-(2-methoxybenzyl)-10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarboxamide (4.74 g) in methylene chloride (100 cc). Stirring is maintained at -50° C. for 45 minutes and then at 20° C. for 48 hours. Saturated aqueous sodium hydrogen carbonate solution (120 cc) is then added cautiously. After stirring until the evolution of carbon dioxide has ceased, the organic phase is separated, washed with distilled water (3×100 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa). The yellow meringue-like residue is purified by chromatography on a column (height: 48 cm; diameter: 2.4 cm) of silica gel (0.06-0.2 mm), eluting with ethyl acetate (2 liters) and collecting 100-cc fractions. Fractions 4 to 15 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The yellow meringue-like residue (2.84 g) is purified by chromatography on a column (height: 33 cm; diameter: 2.4 cm) of silica gel (0.06-0.2 mm), eluting successively with a mixture (50:50 by volume) (250 cc) of cyclohexane and ethyl acetate, then with a mixture (25:75 by volume) (500 cc) of cyclohexane and ethyl acetate and then with ethyl acetate (500 cc) and collecting 60-cc fractions. Fractions 7 to 18 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. to give N-(2-hydroxybenzyl)-10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarboxamide (1.9 g) in the form of a yellow product of meringue-like consistency.

1. stirringStirring
2. waitat 20° C. for 48 hours
3. customthe organic phase is separated
4. washwashed with distilled water (3×100 cc)
5. dry with materialdried over magnesium sulphate
6. filtrationfiltered
7. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa)
8. customThe yellow meringue-like residue is purified by chromatography on a column (height: 48 cm; diameter: 2.4 cm) of silica gel (0.06-0.2 mm)
9. washeluting with ethyl acetate (2 liters)
10. customcollecting 100-cc fractions
11. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
12. customThe yellow meringue-like residue (2.84 g) is purified by chromatography on a column (height: 33 cm; diameter: 2.4 cm) of silica gel (0.06-0.2 mm)
13. washeluting successively with a mixture (50:50 by volume) (250 cc) of cyclohexane and ethyl acetate
14. customwith a mixture (25:75 by volume) (500 cc) of cyclohexane and ethyl acetate and then with ethyl acetate (500 cc) and collecting 60-cc fractions
15. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C.