反应详情

A solution of 2-amino-nicotinic acid ethyl ester (3.60 g, 21.7 mMol) in methanol (100 mL) was treated with HCl gas via sparge tube for 5 minutes, causing the colorless solution to turn yellow. The solution was concentrated in-vacuo, then stripped from methanol (2×50 mL) to remove excess HCl. The residue was dissolved in methanol (100 mL), treated with tert-butyl hypochlorite (2.6 g, 23.8 mMol), and the mixture was allowed to stir overnight at room temperature. Analysis by TLC showed that some starting material remained, so additional tert-butyl hypochlorite (0.47 g, 4.3 mMol) was added, and stirring was continued overnight. Analysis by TLC showed that all starting material had been consumed. The solution was concentrated in-vacuo, the residue was taken up in methylene chloride (150 mL), washed with saturated sodium bicarbonate (3×50 mL), 5% aqueous sodium thiosulfate (3×50 mL), water (50 mL), brine (50 mL), dried over sodium sulfate, and concentrated in-vacuo. The residue was purified over silica gel, eluting with 20%–30% ethyl acetate/heptane, to yield 1.50 g of colorless solids as product. MS (AP+)=201 (M+H)+. Yield=35%.

1. customvia sparge tube for 5 minutes
2. concentrationThe solution was concentrated in-vacuo
3. customto remove excess HCl
4. dissolutionThe residue was dissolved in methanol (100 mL)
5. stirringstirring
6. waitwas continued overnight
7. customhad been consumed
8. concentrationThe solution was concentrated in-vacuo
9. washwashed with saturated sodium bicarbonate (3×50 mL), 5% aqueous sodium thiosulfate (3×50 mL), water (50 mL), brine (50 mL)
10. dry with materialdried over sodium sulfate
11. concentrationconcentrated in-vacuo
12. customThe residue was purified over silica gel
13. washeluting with 20%–30% ethyl acetate/heptane