Lithium Hydroxide → N-benzyl-2-ethynyl-4-methylthiazole-5-carboxamide

Temperature

35 °C

To a solution of N-benzyl-2-bromo-4-methylthiazole-5-carboxamide (0.10 g, 0.32 mmol) in anhydrous toluene (1 mL) was added copper(I) iodide (0.001 g, 0.006 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.005 g, 0.006 mmol), and N,N-diisopropylethylamine (0.17 mL, 0.97 mmol). The reaction mixture was degassed and the reaction flask was filled with nitrogen followed by the addition of trimethylsilylacetylene (0.089 mL, 0.64 mmol). The reaction mixture was heated at 35° C. for 3 hours, cooled to ambient temperature and treated with 1 M aqueous lithium hydroxide (1.0 mL) for 5 minutes, diluted with ethyl acetate (10 mL), washed with water (3 mL) and brine (3 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate:hexanes, 1:1) to afford the title compound as a brown solid (0.035 g, 93%): 1H NMR (300 MHz, CDCl3) δ 7.43-7.21 (m, 5H), 6.17 (t, J=5.7 Hz, 1H), 4.56 (d, J=5.7 Hz, 2H), 3.49 (s, 1H), 2.65 (s, 3H); MS (ES+) m/z 257.2 (M+1).

1. customThe reaction mixture was degassed
2. additionthe reaction flask was filled with nitrogen
3. temperaturecooled to ambient temperature
4. washwashed with water (3 mL) and brine (3 mL)
5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by column chromatography (ethyl acetate:hexanes, 1:1)

ORD record

ord-4b963e15520f4d18af7f06ed71b2bad1

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08258160B2