Thiourea → HCID 178509062, compound

Temperature

50 °C

A slurry of thiourea (92.8 g, 1.22 moles) in EtOH (90 mL) was heated under reflux and vigorously stirred. To this slurry was added a suspension of 3,3-diethoxy-2-formylpropionitrile potassium salt (P-5A) (222.20 g, 1.06 moles) in 25% sodium methoxide/MeOH (85.5 mL, 0.37 mole) and EtOH (285 mL) in five aliquots over a 10 minute period, while maintaining reflux conditions (alternatively, the latter slurry may be heated to 50° C. to give a homogenous solution for the addition). An additional portion of EtOH (150 mL) was added to facilitate stirring. The thick slurry became a bright yellow color following the addition and was held under reflux for an additional 1 hour. The mixture was then cooled and evaporated to near dryness on a rotoevaporator. The residue was dissolved in water (940 mL). Crude product was precipitated from solution by the addition of 30% acetic acid (280 mL) and isolated via filtration using a medium frit sintered glass filtration funnel. The cake was washed with water (800 mL). Purification via trituration in hot water (1 L) for 30 minutes, followed by cooling and filtration gave 118.9 grams (72.3%) of product as a bright yellow solid after drying overnight at 60° C. in a vacuum oven (subsequent preparations have demonstrated that this trituration is unnecessary). An HPLC gave purity as 98.67%. 1H-NMR (DMSO-d6) was consistent with the above desired structure (P-5B).

1. temperatureunder reflux
2. additionTo this slurry was added
3. temperaturewhile maintaining
4. temperaturereflux conditions (alternatively, the latter slurry
5. customto give a homogenous solution
6. additionfor the addition)
7. stirringto facilitate stirring
8. additionthe addition
9. temperatureunder reflux for an additional 1 hour
10. temperatureThe mixture was then cooled
11. customevaporated
12. dissolutionThe residue was dissolved in water (940 mL)
13. customCrude product was precipitated from solution by the addition of 30% acetic acid (280 mL)
14. customisolated via filtration
15. filtrationa medium frit sintered glass filtration funnel
16. washThe cake was washed with water (800 mL)
17. customPurification via trituration in hot water (1 L) for 30 minutes
18. temperatureby cooling
19. filtrationfiltration

ORD record

ord-5da574843660476e873475419f18ec4d

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07320987B2