Hydrochloric Acid → HCID 21998640, compound

HRID 1976556Notes

Reaction equation

HRID 1976556 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:17]=[CH:18][C:19]=1[O:20][CH3:21])[CH2:12][NH:13][C:14]([NH2:16])=[S:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC([O-])(C)C.[K+].[C:28]([CH2:30][C:31](OCC)=[O:32])#[N:29].Cl>C(O)(C)C.CC(C)=O.O>[NH2:29][C:28]1[N:13]([CH2:12][C:11]2[CH:17]=[CH:18][C:19]([O:20][CH3:21])=[C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:10]=2)[C:14](=[S:15])[NH:16][C:31](=[O:32])[CH:30]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7764Ethyl cyanoacetate2×HCID 21998619HCID 21998619, compoundHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 21998640HCID 21998640, compoundYield 74.1%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

1-(3-Benzyloxy-4-methoxy-benzyl)-2-thiourea (72.58 g, 240 mmole) was added to a solution of 97% t-BuOK (30.54 g, 264 mmole) in isopropanol (300 ml), the mixture heated under reflux until dissolution was complete, then ethyl cyanoacetate (26.1 .ml, 245 mmole) was added. After 5 hours at reflux, the mixture was cooled slightly, another batch of t-BuOK (2.78 g, 24 mmole) and ethyl cyanoacetate (5.12 ml, 48 mmole) was added, and the mixture heated under reflux for a further 15 hours. The reaction mixture was cooled to room temperature, poured onto water (1.21) and neutralized with cooling to pH 8 with 5M HCl (43 ml). After 1 hour stirring the solid was collected at 10° C. and washed first with water (180 ml), then saturated sodium bicarbonate solution (60 ml), isopropanol (60 ml) and finally cold water (500 ml). The crude material was suspended in 0.5M NaOH (1.4 l) and isopropanol (350 ml). The insoluble part was filtered off and washed with 0.1M NaOH and water to give recovered thiourea (10.45 g, 14.4%). The filtrate was neutralized to pH 8 with 2M phosphoric acid (175 ml ), crystallized over night, the solid collected and washed with the above three component liqours and water to give the crude thiouracil (73.33 g). This product was suspended in hot acetone (600 ml), concentrated to 500 ml and collected at 0-5° C. to give 6-amino-1-(3-benzyloxy-4-methoxy-benzyl)-2-thiouracil (65.73 g, 74.1%), mp 239-240° C.

Workup

  1. temperaturethe mixture heated
  2. temperatureunder reflux until dissolution
  3. temperatureAfter 5 hours at reflux
  4. temperaturethe mixture was cooled slightly
  5. temperaturethe mixture heated
  6. temperatureunder reflux for a further 15 hours
  7. customwas collected at 10° C.
  8. washwashed first with water (180 ml)
  9. filtrationThe insoluble part was filtered off
  10. washwashed with 0.1M NaOH and water
  11. customto give
  12. customrecovered thiourea (10.45 g, 14.4%)
  13. customcrystallized over night
  14. customthe solid collected
  15. washwashed with the above three component liqours and water
  16. customto give the crude thiouracil (73.33 g)
  17. concentrationconcentrated to 500 ml
  18. customcollected at 0-5° C.

Sources & evidence

ORD record
ord-0afc157a44d64c89a3a2d14bd34fb4e5
Source dataset
uspto-grants-2001_05
Patent number
US06228859B1

Reaction notes

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