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

HRID 1358231Notes

Reaction equation

HRID 1358231 reaction equation
C(OCC)(=O)C(OCC)=O.COC1C=CC(N2CCOCC2)=CC=1N.C([O:28][C:29](=[O:47])[C:30]([NH:32][C:33]1[CH:38]=[C:37]([N:39]2[CH2:44][CH2:43][O:42][CH2:41][CH2:40]2)[CH:36]=[CH:35][C:34]=1[O:45][CH3:46])=O)C.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:49]>C1(C)C(C)=CC=CC=1>[CH3:46][O:45][C:34]1[CH:35]=[CH:36][C:37]([N:39]2[CH2:44][CH2:43][O:42][CH2:41][CH2:40]2)=[CH:38][C:33]=1[NH:32][C:30](=[S:49])[C:29]([OH:28])=[O:47]

Participants

6

Reactant 4

HCID 7268Diethyl OxalateHCID 14817Phosphorus sulfide (P2S5)HCID 113677782-Methoxy-5-morpholinoanilineHCID 21137088HCID 21137088, compound

Product 1

HCID 21919264(2-Methoxy-5-morpholin-4-yl-phenylamino)-thioxo-acetic acid

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Conditions

Temperature
180 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-79284924ba0b468a8da2df95e109c531
Source dataset
uspto-grants-2003_07
Patent number
US06596718B1

Reaction notes

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