Methanol → Methyl 2-hydroxy-2-(2-phenyl-1,3-thiazol-4-yl)acetate

Temperature

0 °C

Under a nitrogen atmosphere, trimethylsilylcyanide (824 μL, 6.6 mmol) was added at 0° C. to a solution of 2-phenyl-1,3-thiazole-4-carbaldehyde (1 g, 5.28 mmol) and zinc iodide (II) (166 mg, 0.52 mmol) in dichloromethane (30 mL). After 6 hours, the reaction mixture was quenched with a saturated aqueous solution of sodium bicarbonate and extracted with dichloromethane (2×20 mL). The organic layer was washed with brine (10 mL), dried over sodium sulfate, filtered, and evaporated under reduced pressure. The residue was used for the hydrolysis without further purification. Then, 2-(2-phenyl-1,3-thiazol-4-yl)-2-[(trimethylsilyl)oxy]acetonitrile was dissolved in anhydrous methanol (30 mL) and cooled at 0° C. and hydrogen chloride was bubbled for 2 minutes. The mixture was then warmed at room temperature for 20 h and concentrated under vacuum. A saturated solution of sodium bicarbonate (10 mL) was added to the residue and extracted with dichloromethane (2×15 mL). The organic layer was washed with brine (10 mL), dried over sodium sulfate, filtered, and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 70/30) to afford the desired alcohol (6a) as a white yellow oil (950 mg, 3.81 mmol, 72%).

1. customthe reaction mixture was quenched with a saturated aqueous solution of sodium bicarbonate
2. extractionextracted with dichloromethane (2×20 mL)
3. washThe organic layer was washed with brine (10 mL)
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. customevaporated under reduced pressure
7. customThe residue was used for the hydrolysis without further purification
8. customhydrogen chloride was bubbled for 2 minutes
9. temperatureThe mixture was then warmed at room temperature for 20 h
10. concentrationconcentrated under vacuum
11. additionA saturated solution of sodium bicarbonate (10 mL) was added to the residue
12. extractionextracted with dichloromethane (2×15 mL)
13. washThe organic layer was washed with brine (10 mL)
14. dry with materialdried over sodium sulfate
15. filtrationfiltered
16. customevaporated under reduced pressure
17. customThe residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 70/30)

ORD record

ord-5cf73372d08f41b8829643a584d6720f

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09238026B2