反应详情

A solution of oxalyl chloride in dichloromethane (2 M, 100 mL, 200 mmol) was added dropwise to a stirred solution of trans-4-bromocinnamic acid [CAS 1200-07-3] (25.0 g, 110 mmol) and DMF (0.5 mL) in dichloromethane (300 mL) at 0° C. under a dry nitrogen atmosphere. The nitrogen line and cooling bath were removed and the mixture was stirred at room temperature until gas evolution had ceased. Volatiles were removed under reduced pressure, and the residue was redissolved in dichloromethane (200 mL). The resulting solution was added dropwise to a stirred solution of N,O-dimethylhydroxylamine hydrochloride (21.5 g, 220 mmol) and triethylamine (61.4 mL, 440 mmol) in dichloromethane (150 mL) at 0° C. When the addition was complete, the cooling bath was removed and the mixture was stirred overnight at room temperature. Insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was partitioned between ethyl acetate and aqueous 10% citric acid. The organic layer was successively washed with aqueous 10% citric acid, aqueous 3 N sodium hydroxide, and brine. The ethyl acetate solution was then dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (65:35 hexane/ethyl acetate) to provide the title compound. 1H NMR (300 MHz, CDCl3): δ 3.31 (s, 3H), 3.76 (s, 3H), 7.02 (d, J=15 Hz, 1H), 7.43 (d, J=9 Hz, 2H), 7.51 (d, J=9 Hz, 2H), 7.67 (d, J=9 Hz, 1H). MS (DCl—NH3) m/z 270 (M+H)+, m/z 287 (M+NH4)+.

1. temperatureThe nitrogen line and cooling bath
2. customwere removed
3. customVolatiles were removed under reduced pressure
4. dissolutionthe residue was redissolved in dichloromethane (200 mL)
5. additionWhen the addition
6. customthe cooling bath was removed
7. stirringthe mixture was stirred overnight at room temperature
8. customInsoluble material was removed by filtration
9. concentrationthe filtrate was concentrated under reduced pressure
10. customThe residue was partitioned between ethyl acetate and aqueous 10% citric acid
11. washThe organic layer was successively washed with aqueous 10% citric acid, aqueous 3 N sodium hydroxide, and brine
12. dry with materialThe ethyl acetate solution was then dried (MgSO4)
13. filtrationfiltered
14. concentrationThe filtrate was concentrated under reduced pressure
15. customthe residue was purified by column chromatography (65:35 hexane/ethyl acetate)