反应详情

4-(2,3-dimethoxybenzoyl)-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester (7) (˜0.1128 mol) was cooled to 0° C., treated with trifluoroacetic acid (85 mL), and stirred at ambient temperature for 1 hour. Following concentration in vacuum, the material was dissolved in water (300 mL), washed with hexane (2×110 mL) and then treated with solid sodium hydroxide (18 g). The resulting aqueous solution was then extracted with methylene chloride (3×170 mL). The combined organic extracts were washed with brine (220 mL), dried (MgSO4) and concentrated in vacuum. The resulting residue was dissolved in ethanol (110 mL), cooled to 0° C., treated with anhydrous hydrogen chloride gas until acidic, diluted with ether (110 mL) and stirred for 1 hour. The resulting solid was collected by filtration, then washed with a mixture of ethanol and ether (1:1, 110 mL) to afford 4-(2,3-dimethoxybenzoyl)piperidine (16) hydrochloride salt as a white solid (19.18 g, 53%).

1. concentrationconcentration in vacuum
2. dissolutionthe material was dissolved in water (300 mL)
3. washwashed with hexane (2×110 mL)
4. additiontreated with solid sodium hydroxide (18 g)
5. extractionThe resulting aqueous solution was then extracted with methylene chloride (3×170 mL)
6. washThe combined organic extracts were washed with brine (220 mL)
7. dry with materialdried (MgSO4)
8. concentrationconcentrated in vacuum
9. dissolutionThe resulting residue was dissolved in ethanol (110 mL)
10. temperaturecooled to 0° C.
11. additiontreated with anhydrous hydrogen chloride gas until acidic,
12. additiondiluted with ether (110 mL)
13. stirringstirred for 1 hour
14. filtrationThe resulting solid was collected by filtration
15. washwashed with a mixture of ethanol and ether (1:1, 110 mL)