Iodine → 2-Iodo-6-(trifluoromethyl)pyrazine

A three liter flask was charged with a solution of 2-amino-6-trifluoromethylpyrazine (obtained by the method of J. L. Miesel, U.S. Pat. No. 4,293,552, 95% pure by HPLC analysis, 32.6 g, 0.20 mol) in chloroform (1000 mL). Freshly ground iodine (101 g. 0.40 mol) was added to give a dark purple solution. After 40 min, a solution of t-butyl nitrite (22.9 g, 0.20 mol) in chloroform (300 mL) was added dropwise over 1 h. During the addition, slow gas evolution was observed together with a mild exotherm (<10° C.) which was moderated with a cold water bath. After an additional 1 h at room temperature the reaction mixture was washed with saturated aqueous sodium sulfite (3×500 mL) to remove the excess iodine. The chloroform solution was dried over magnesium sulphate, filtered and concentrated on a Buchi to give 23 g of an orange oil. The crude product was purified by distillation from copper (40-80 mesh, 200 mg) to give 19.5 g of the title compound as a yellow oil; b.p. 50°-56° C./0.6 mmHg; δ (360 MHz, CDCl3) 9.06 (1H, s, pyrazine-H), 8.86 (1H, s, pyrazine-H); m/e 274 (M+).

1. customobtained by the method of J
2. customto give a dark purple solution
3. additionDuring the addition, slow gas evolution
4. customwas observed together with a mild exotherm (<10° C.) which
5. customwas moderated with a cold water bath
6. washAfter an additional 1 h at room temperature the reaction mixture was washed with saturated aqueous sodium sulfite (3×500 mL)
7. customto remove the excess iodine
8. dry with materialThe chloroform solution was dried over magnesium sulphate
9. filtrationfiltered
10. concentrationconcentrated on a Buchi

ORD record

ord-c6a0fb1f38694b13add44eef6c2b8361

Source dataset

uspto-grants-1995_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05384408