反应详情

A suspension of 1-methyl-2-piperidone (5.0 g) in 4N sodium hydroxide (22.1 ml) was heated and stirred for 8.5 hours under reflux. After the suspension was cooled to room temperature, conc. hydrochloric acid (7.4 ml) was added. A solution of sodium carbonate (9.4 g) and 5-bromo-4-fluorobenzaldehyde (4.5 g) in DMSO (74 ml) was added, and the resulting mixture was stirred for 1.5 hours under reflux. The mixture was allowed to cool to room temperature, and adjusted to pH of about 3.3 with 6N hydrochloric acid. After extraction with ethyl acetate, the organic layer was washed with saturated salt water, dried over anhydrous sodium sulfate, and concentrated. The precipitated crystal obtained was redissolved in isopropylether [IPE] (20 ml) under heating, and the solution was allowed to cool to room temperature, and stirred for 1 hour at 0° C. The crystal obtained was filtered and washed with IPE. Drying under reduced pressure (40° C., 1 hour) gave yellow crystal of 5-(4-bromo-2-formyl-N-methylanilino)pentanoic acid (4.0 g, yield 57%).

1. temperaturewas heated
2. temperatureunder reflux
3. stirringthe resulting mixture was stirred for 1.5 hours
4. temperatureunder reflux
5. temperatureto cool to room temperature
6. extractionAfter extraction with ethyl acetate
7. washthe organic layer was washed with saturated salt water
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated
10. customThe precipitated crystal obtained
11. temperatureunder heating
12. temperatureto cool to room temperature
13. stirringstirred for 1 hour at 0° C
14. customThe crystal obtained
15. filtrationwas filtered
16. washwashed with IPE
17. customDrying under reduced pressure (40° C., 1 hour)