反应详情

温度

-78 °C

To a stirred solution of diisopropylamine (8.81 g, 87.0 mmol) in tetrahydrofuran (300 ml) at 0° C. was added 1.6M n-butyllithium in hexanes (54 ml, 86.4 mmol) over a 10 minute period. The resulting yellow mixture was stirred for 30 minutes, cooled to -78° C. and hexamethylphosphoramide (15.5 g, 86.2 mmol) was added. To this mixture was added ethyl N-(diphenylmethylene) glycinate (23.0 g, 86.0 mmol) in tetrahydrofuran (100 ml) over a 20 minute period. The dark orange mixture was stirred for 1 hour and then a solution of 2-bromomethyl-5-nitrothiophene (19.0 g, 85.6 mmol) in tetrahydrofuran (100 ml) was added over a 20 minute period. The mixture was stirred for 1 hour and then warmed to 0° C. After quenching with approximately 150 ml of ice-cold water, the mixture was concentrated at reduced pressure. The remaining aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine and dried over magnesium sulphate. The solvent was removed at reduced pressure and the resulting dark brown oil was filtered through silica gel eluting with 25% ethyl acetate/hexane to remove excess diisopropylamine . The filtrate was concentrated at reduced pressure and the resulting dark brown oil was placed in vacuo overnight. Ethyl N-diphenylmethylene-3-(5-nitro-2-thienyl)-DL-alaninate (35.3 g) was obtained as a viscous dark brown oil. The product was used without further purification.

1. stirringThe dark orange mixture was stirred for 1 hour
2. stirringThe mixture was stirred for 1 hour
3. temperaturewarmed to 0° C
4. customAfter quenching with approximately 150 ml of ice-cold water
5. concentrationthe mixture was concentrated at reduced pressure
6. extractionThe remaining aqueous layer was extracted twice with ethyl acetate
7. washThe combined organic layers were washed with brine
8. dry with materialdried over magnesium sulphate
9. customThe solvent was removed at reduced pressure
10. filtrationthe resulting dark brown oil was filtered through silica gel eluting with 25% ethyl acetate/hexane
11. customto remove excess diisopropylamine
12. concentrationThe filtrate was concentrated at reduced pressure
13. customwas placed in vacuo overnight