Boron trifluoride etherate → Ethyl 4-isopropylthiazole-5-carboxylate

Temperature

0 °C

To a 0° C. solution of ethyl 2-amino-4-(propan-2-yl)-1,3-thiazole-5-carboxylate (3.6 g, 16.7 mmol) in anhydrous THF (60 mL) was added boron trifluoride diethyl etherate (3.0 mL, 23.9 mmol). After 15 minutes of stirring at 0° C., tert-butyl nitrite (10 mL, 84 mmol) was added. The mixture was stirred at 0° C. for 4 hours before more tert-butyl nitrite (10 mL, 84 mmol) was added. The mixture was stirred at 0° C. for 1 hour before a solution of sodium hypophosphonate (6.2 g, 70.1 mmol) in water (20 mL) was added. The mixture was stirred at 0° C. for 2 hours and at room temperature overnight. The solution was basified to pH 9-10 with 5N NaOH and was extracted with EtOAc (3×60 mL). The organic extracts were combined, extracted with brine (1×100 mL), dried over MgSO4, filtered, evaporated, and dried in vacuo, affording ethyl 4-(propan-2-yl)-1,3-thiazole-5-carboxylate (2.1 g, 63% yield). The product was used without further purification.

1. additionwas added
2. additionwas added
3. stirringThe mixture was stirred at 0° C. for 2 hours and at room temperature overnight
4. extractionwas extracted with EtOAc (3×60 mL)
5. extractionextracted with brine (1×100 mL)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. customevaporated
9. customdried in vacuo

ORD record

ord-354af2baa1f743a29b59ecbbb1bcd6b2

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09315521B2