Diethyl Oxalate → (2-Methoxy-5-morpholin-4-yl-phenylamino)-thioxo-acetic acid

Temperature

180 °C

In accordance with scheme 1, the compounds of formula I are prepared as follows: Diethyl oxalate (2) is heated to about 120° C. 2-Methoxy-5-morpholin-4-yl-phenylamine (1) is added very cautiously in small quantities and the mixture is heated for 90 minutes at about 180° C. After cooling to room temperature and filtration n-hexane is added. The resulting precipitate is collected by filtration. After washing with hexane and drying N-(2-methoxy-5-morpholin-4-yl-phenyl)-oxalamic acid ethyl ester (3) is obtained. Then, to the obtained compound of formula (3) in boiling xylene is added phosphorus pentasulfide in small portions over a period of about 30 minutes. The mixture is refluxed for about 5 hours, cooled to room temperature and filtered. The solution is extracted with 1N NaOH. The aqueous phase is washed with toluene, filtered, and treated at 0-5° C. with concentrated hydrochloric acid until pH 1 was reached. Filtration of the precipitate yielded (2-methoxy-5-morpholin-4-yl-phenylamino)-thioxo-acetic acid (4).

1. customIn accordance with scheme 1, the compounds of formula I are prepared
2. temperatureAfter cooling to room temperature
3. filtrationfiltration n-hexane
4. additionis added
5. filtrationThe resulting precipitate is collected by filtration
6. washAfter washing with hexane
7. dry with materialdrying N-(2-methoxy-5-morpholin-4-yl-phenyl)-oxalamic acid ethyl ester (3)
8. customis obtained
9. temperatureThe mixture is refluxed for about 5 hours
10. temperaturecooled to room temperature
11. filtrationfiltered
12. extractionThe solution is extracted with 1N NaOH
13. washThe aqueous phase is washed with toluene
14. filtrationfiltered
15. additiontreated at 0-5° C. with concentrated hydrochloric acid until pH 1
16. filtrationFiltration of the precipitate

ORD record

ord-79284924ba0b468a8da2df95e109c531

Source dataset

uspto-grants-2003_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06596718B1