Hydrochloric Acid → HCID 19913634, compound

HRID 2072776Notes

Reaction equation

HRID 2072776 reaction equation
B.[NH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[O:14][CH2:13][C:12](=O)[N:11]([CH:16]([CH3:18])[CH3:17])[CH2:10]2)=[CH:5][C:4]=1[C:19]#[N:20].CO.[ClH:23]>O1CCCC1>[ClH:23].[NH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[O:14][CH2:13][CH2:12][N:11]([CH:16]([CH3:18])[CH3:17])[CH2:10]2)=[CH:5][C:4]=1[C:19]#[N:20]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 6331BoraneHCID 19913626HCID 19913626, compound

Product 1

HCID 19913634HCID 19913634, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Borane in tetrahydrofuran (1.0M solution; 7.5 ml) was added dropwise, at ambient temperature, to a stirred solution of 2-[4-amino-3-cyanophenyl]-4-[1-methylethyl]-5-oxomorpholine (0.83 g) in dry tetrahydrofuran (60 ml) under nitrogen. The mixture was then heated under reflux with stirring, under nitrogen, for three hours, cooled and methanol (4 ml) in tetrahydrofuran (10 ml) added carefully. The mixture was heated under reflux for one hour, cooled, hydrogen chloride gas passed and the mixture heated under reflux for one hour. After cooling and evaporation to dryness, the residue was dissolved in dilute hydrochloric acid, washed with diethyl ether, the aqueous phase made alkaline by addition of dilute aqueous sodium hydroxide and extracted with dichloromethane. The dichloromethane extracts were washed with brine, dried over anhydrous magnesium sulphate, filtered and the filtrate evaporated to dryness. The residual oil was purified by chromatography on silica gel using 2-3% methanol in dichloromethane as eluant. Conversion to its hydrochloride salt by addition of ethereal hydrogen chloride and recrystallisation from acetone-diethyl ether gave the title compound, m.p. 200°-2° C., as a white solid.

Workup

  1. temperatureThe mixture was then heated
  2. temperatureunder reflux
  3. temperaturecooled
  4. temperatureThe mixture was heated
  5. temperatureunder reflux for one hour
  6. temperaturecooled
  7. temperaturethe mixture heated
  8. temperatureunder reflux for one hour
  9. temperatureAfter cooling
  10. customevaporation to dryness
  11. dissolutionthe residue was dissolved in dilute hydrochloric acid
  12. washwashed with diethyl ether
  13. additionby addition of dilute aqueous sodium hydroxide
  14. extractionextracted with dichloromethane
  15. washThe dichloromethane extracts were washed with brine
  16. dry with materialdried over anhydrous magnesium sulphate
  17. filtrationfiltered
  18. customthe filtrate evaporated to dryness
  19. customThe residual oil was purified by chromatography on silica gel using 2-3% methanol in dichloromethane as eluant
  20. additionConversion to its hydrochloride salt by addition of ethereal hydrogen chloride and recrystallisation from acetone-diethyl ether

Sources & evidence

ORD record
ord-8ad2345c8fe9484b9c405977cf62cd47
Source dataset
uspto-grants-1990_04
Patent number
US04914202

Reaction notes

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