Hydrochloric Acid → HCID 178471102, compound

Ethyl diethoxyacetate (10.4 mL, 60.0 mmol) and EtOAc (9.0 mL, 90 mmol) were heated at 85° C. and then treated with sodium metal (1.44 g, 60 mmol) in small pieces. After 2 h of heating, an additional portion of EtOAc was added (9.0 mL, 90 mmol) followed by an additional portion of sodium metal (1.44 g, 60 mmol), and heating was maintained for an additional 3 h. The reaction was then cooled to room temperature and stirred overnight. The reaction was then poured onto water, acidified with 1 N HCl, and extracted with diethyl ether (3×). The organics were washed with saturated NaHCO3 (3×) and saturated NaCl, dried over MgSO4, and concentrated in vacuo. The crude product was dried under vacuum (0.5 mm Hg) while being heated in an oil bath at 80° C. to remove any ethyl acetoacetate that may have been produced. To a solution of the crude keto ester and thiourea (4.57 g, 60 mmol) in EtOH (45 mL), was added 25% NaOMe (13 mL, 57 mmol, Aldrich) and heated at reflux for 4 h. The reaction was cooled for 10 minutes, diluted with water (50 mL), treated with benzyl bromide (9.4 g, 55 mmol), and then stirred warm. Crystals formed after 5 minutes, and the reaction was allowed to cool to room temperature and sit undisturbed for 1 h. The white solid was diluted with water and filtered to give 2-benzylsulfanyl-6-diethoxymethyl-pyrimidin-4-ol (9.5 g, 29.6 mmol, 50%).

1. temperatureAfter 2 h of heating
2. temperatureheating
3. temperaturewas maintained for an additional 3 h
4. additionThe reaction was then poured onto water
5. extractionextracted with diethyl ether (3×)
6. washThe organics were washed with saturated NaHCO3 (3×) and saturated NaCl
7. dry with materialdried over MgSO4
8. concentrationconcentrated in vacuo
9. dry with materialThe crude product was dried under vacuum (0.5 mm Hg)
10. temperaturewhile being heated in an oil bath at 80° C.
11. customto remove any ethyl acetoacetate that
12. custommay have been produced
13. temperatureheated
14. temperatureat reflux for 4 h
15. temperatureThe reaction was cooled for 10 minutes
16. stirringstirred
17. temperaturewarm
18. customCrystals formed after 5 minutes
19. temperatureto cool to room temperature
20. waitsit undisturbed for 1 h
21. filtrationfiltered

ORD record

ord-f142ad52ac244529a6a519e369a74b4d

Source dataset

uspto-grants-2005_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06846828B2