Chloroacetyl chloride → N-benzyl-N-(4-thiazolylmethyl)chloroacetamide

4-Chloromethylthiazole (1.33 g, 10.0 mmol) and benzylamine (2.2 mL, 20.0 mmol) were mixed together and heated to 80° C. for 24 hours and allowed to cool to room temperature. The solid mass was treated with 2M aqueous sodium carbonate and stirred until the mass was broken up and the mixture was extracted with 2 portions of ethyl ether. The combined organic extracts were dried (Na2SO4), filtered, and concentrated. The residue was dissolved in 40 mL of dichloromethane, cooled to 0° C., and 40 mL of saturated, aqueous NaHCO3 was added. To this stirred biphasic mixture was added chloroacetyl chloride (1.8 mL, 22.0 mmol) dropwise and mixture was stirred for an additional 2 hours at 0° C. The layers were separated and the organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (silica gel, 30% -50% ethyl acetate/hexanes) to provide first, 0.58 g (21%) N-benzylchloroacetamide followed by 0.76 g (27%) of the title compound.

1. temperatureto cool to room temperature
2. extractionthe mixture was extracted with 2 portions of ethyl ether
3. dry with materialThe combined organic extracts were dried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated
6. dissolutionThe residue was dissolved in 40 mL of dichloromethane
7. temperaturecooled to 0° C.
8. addition40 mL of saturated, aqueous NaHCO3 was added
9. stirringmixture was stirred for an additional 2 hours at 0° C
10. customThe layers were separated
11. dry with materialthe organic phase was dried (Na2SO4)
12. filtrationfiltered
13. concentrationconcentrated
14. customThe residue was purified by column chromatography (silica gel, 30% -50% ethyl acetate/hexanes)
15. customto provide first

ORD record

ord-ca9b010d87f24aa6a048ebdf060cc5ba

Source dataset

uspto-grants-2001_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06277871B1