反应详情

The ephedrine salt product of Example 53(b) (425 mg., 1.22 mmol) was partitioned between ethyl ether (100 mL) and dilute HCl (1.22 mL of 1N HCl in 100 mL of water). The ether layer was washed with water (2×100 mL), dried (MgSO4), and concentrated. The residue was coevaporated from methylene chloride (2×20 mL). The free acid was dissolved in methylene chloride (3 mL) and oxalyl chloride (0.107 mL, 1.22 mmol) was added. Dimethylformamide (0.011 mL, 0.012 mmol) was added and the mixture was stirred at room temperature for 2 hours. Concurrently bis (trimethylsilyl)trifluoroacetamide (0.75 mL, 2.8 mmol) was added to a suspension of the product from Example 57 (f) (465 mg.) in acetonitrile. While stirring for 2.5 hours, this suspension became a light yellow solution. This mixture was cooled to 0° C. and the above acid chloride solution was added in one portion. After warming to room temperature, the mixture was stirred for 18 hours. The reaction mixture was partitioned between ethyl acetate (75 mL) and 1N HCl (75 mL). The ethyl acetate layer was washed with 1N HCl (75 mL), water (75 mL), and brine (75 mL). The organic layer was then dried (MgSO4), concentrated, and coevaporated from toluene (2×10 mL). The residue was chromatographed on a 2.5×20 cm silica gel column using 1 L hexane:ethyl acetate:acetic acid (70:30:2) and 1 L hexane:ethyl acetate:acetic acid (60:40:2) as the mobile phase. The pure fractions were concentrated and the residue coveaporated from heptane to afford 270 mg. of tan solid which was recrystallized from ethyl acetate/hexane. Filtration and washing with heptane afforded 203 mg. of the (S,S) title A compound as a white solid, m.p. 139°-140° C., TLC Rf =0.10 (ethyl acetate:hexane:acetic acid, 50:50:2).

1. washThe ether layer was washed with water (2×100 mL)
2. dry with materialdried (MgSO4)
3. concentrationconcentrated
4. dissolutionThe free acid was dissolved in methylene chloride (3 mL)
5. stirringWhile stirring for 2.5 hours
6. temperatureThis mixture was cooled to 0° C.
7. temperatureAfter warming to room temperature
8. stirringthe mixture was stirred for 18 hours
9. customThe reaction mixture was partitioned between ethyl acetate (75 mL) and 1N HCl (75 mL)
10. washThe ethyl acetate layer was washed with 1N HCl (75 mL), water (75 mL), and brine (75 mL)
11. dry with materialThe organic layer was then dried (MgSO4)
12. concentrationconcentrated
13. customThe residue was chromatographed on a 2.5×20 cm silica gel column
14. concentrationThe pure fractions were concentrated
15. customto afford 270 mg
16. customof tan solid which was recrystallized from ethyl acetate/hexane
17. filtrationFiltration
18. washwashing with heptane
19. customafforded 203 mg