丙酰胺 → 2-(2-Ethyl-4-methyl-thiazol-5-yl)-ethanol

Propionamide (20 grams, 0.27 moles) and dried THF (150 grams) were added to a 500 ml three-neck flask equipped with a mechanical stirrer, a condenser and a thermometer. The mixture was stirred and 18 grams of phosphorus pentasulfide (0.08 moles) were added over a time period of 30 minutes while keeping the temperature between 20–25° C. The reaction mixture was then refluxed for 2 hours and was thereafter cooled to room temperature. 57.8 grams of 5-acetoxy-3-chloro-2-pentanone were then added, over a time period of 15 minutes, and the reaction mixture was allowed to reflux for 20 hours. Thereafter, the THF was removed by distillation at atmospheric pressure, the reaction mixture was cooled to 25° C., 120 grams of hydrochloric acid (10%) were added, and the mixture was brought back to reflux for 1 additional hour. After cooling to room temperature the reaction mixture was extracted with two portions of 50 grams of dichloromethane to remove excess starting materials. The acidic aqueous phase was turned basic with a 20% aqueous solution of sodium hydroxide and the resulting thiazole was extracted with three portions of 75 grams of dichloromethane. The dichloromethane extracts were combined and dried over sodium sulfate, filtered and evaporated to dryness. The residue was distilled under vacuum at 0.5 mmHg to yield 20 grams of pale yellow oil (43.3% yield) having a purity of 98.9%, as determined by gas chromatography.

1. customequipped with a mechanical stirrer, a condenser
2. custombetween 20–25° C
3. temperatureThe reaction mixture was then refluxed for 2 hours
4. temperatureto reflux for 20 hours
5. customThereafter, the THF was removed by distillation at atmospheric pressure
6. temperaturethe reaction mixture was cooled to 25° C.
7. addition120 grams of hydrochloric acid (10%) were added
8. temperatureto reflux for 1 additional hour
9. temperatureAfter cooling to room temperature the reaction mixture
10. extractionwas extracted with two portions of 50 grams of dichloromethane
11. customto remove excess starting materials
12. extractionthe resulting thiazole was extracted with three portions of 75 grams of dichloromethane
13. dry with materialdried over sodium sulfate
14. filtrationfiltered
15. customevaporated to dryness
16. distillationThe residue was distilled under vacuum at 0.5 mmHg

ORD记录

ord-a138d221c0494dc98a8ddf6b10fd417a

来源数据集

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

专利号

US07189750B2