Acetaldehyde → Methyl 2-amino-5-methyl-1,3-thiazole-4-carboxylate

Temperature

0 °C

Sodium methoxide (25% wt solution, 50 mL) was added slowly to a 0° C. solution of methyl 2,2-dichloroacetate (25 mL, 261 mmol) and acetaldehyde (15 mL, 267 mmol) in 200 mL diethyl ether. The mixture was stirred at 0° C. for 1 hour. Water (100 mL) was added, and the organic layer was recovered. The aqueous phase was extracted with diethyl ether (2×100 mL). The organic extracts were combined, washed with brine (2×200 mL), dried over MgSO4, filtered, evaporated, and dried in vacuo. The crude oil (29 g) was dissolved in MeOH (250 mL), and thiourea (15.5 g, 190 mmol) was added. The solution was stirred at reflux for 4 hours. After cooling to room temperature, the solvent was evaporated. The oily residue was dissolved in MeOH (50 mL). The solution was poured into ice/water (500 mL). The pH was brought to approximately 8-9 with concentrated ammonium hydroxide. The yellow solid material was recovered by filtration, washed with water (3×50 mL) and hexanes (3×50 mL), and dried in vacuo, affording methyl 2-amino-5-methyl-1,3-thiazole-4-carboxylate (11.7 g, 26%) as a yellow solid. The product was used without further purification.

1. customthe organic layer was recovered
2. extractionThe aqueous phase was extracted with diethyl ether (2×100 mL)
3. washwashed with brine (2×200 mL)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. customevaporated
7. customdried in vacuo
8. dissolutionThe crude oil (29 g) was dissolved in MeOH (250 mL)
9. stirringThe solution was stirred
10. temperatureat reflux for 4 hours
11. temperatureAfter cooling to room temperature
12. customthe solvent was evaporated
13. dissolutionThe oily residue was dissolved in MeOH (50 mL)
14. additionThe solution was poured into ice/water (500 mL)
15. filtrationThe yellow solid material was recovered by filtration
16. washwashed with water (3×50 mL) and hexanes (3×50 mL)
17. customdried in vacuo

ORD record

ord-dd202fa9b7c7447d94eb802fa3fe1595

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09040538B2