Dimethylformamide → 2-(Dimethylamino)-1,3-thiazole-5-carbaldehyde

Temperature

-78 °C

To a solution of 2-chlorothiazole (300 mg, 2.51 mmol) in distilled tetrahydrofuran (4 mL) at −78° C. was added n-butyllithium (2.5M solution in hexane, 2.58 mmol, 1.03 mL) slowly dropwise. After stirring 10 min at −78° C., N,N-dimethylformamide (2.76 mmol, 0.213 mL) was added and the reaction was warmed slowly to room temperature over 2 h. The reaction mixture was quenched with water (80 μL) and stirred for 24 h at room temperature. After the volatiles were removed under reduced pressure, the residue was diluted with water (25 mL) and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with brine (25 mL), dried (MgSO4), filtered, concentrated under reduced pressure. The residue was flash chromatographed (silica gel, 50% ethyl acetate in petroleum ether) to yield 2-(dimethylamino)thiazole-5-carboxaldehyde (170 mg, 43% yield) as an orange solid.

1. temperaturethe reaction was warmed slowly to room temperature over 2 h
2. customThe reaction mixture was quenched with water (80 μL)
3. stirringstirred for 24 h at room temperature
4. customAfter the volatiles were removed under reduced pressure
5. additionthe residue was diluted with water (25 mL)
6. extractionextracted with ethyl acetate (2×100 mL)
7. washThe combined organic layers were washed with brine (25 mL)
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customchromatographed (silica gel, 50% ethyl acetate in petroleum ether)

ORD record

ord-8c8590ddde204fafa4a4275ad112a509

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06515124B2