Trifluoroacetic acid → 6-Chloro-4-iodo-2-methoxy-3-(2-butenyloxymethyl)pyridine

Temperature

0 °C

A three-necked 500-mL round-bottom flask is equipped with a mechanical stirrer. Under nitrogen, the flask is charged with 6-chloro-4-iodo-2-methoxypyridine-3-carbaldehyde (53.0 g, 178 mmol) obtained as prepared in U.S. Pat. No. 5,254,690 to Comins et al. issued Oct. 19, 1993, triethylsilane (42.7 mL, 267 mmol) and crotyl alcohol (60.8 mL, 713 mmol). The slurry is cooled to 0° C. and trifluoroacetic acid (90.0 mL, 1.17 mmol) is added over 1 h. The reaction is allowed to warm to ambient temperature and stirred for 16 h. The reaction mixture is slowly poured into a rapidly stirred solution of saturated sodium bicarbonate in water (1.5 L). The mixture is extracted with methyl t-butyl ether (4×300 mL). The combined organic layers are washed with brine (700 mL) and dried over anhydrous sodium sulfate (150 g). The drying agent is removed by filtration and the solvents are removed in vacuo to afford 6-chloro-4-iodo-2-methoxy-3-(2-butenyloxymethyl)pyridine as crude product. The product can be purified by vacuum distillation to provide 6-chloro-4-iodo-2-methoxy-3-(2-butenyloxymethyl)pyridine as a light yellow oil. 1H NMR (200 MHz, CDCL3) δ1.75 (d, J=6.1 Hz, 3H), 3.92 (s, 3H), 4.00 (m, 2H), 4.59 (s, 2H), 5.74 (m, 1H) 5.75 (m, 1H), 7.39 (s, 1H).

1. customA three-necked 500-mL round-bottom flask is equipped with a mechanical stirrer
2. customobtained
3. customas prepared in U.S
4. temperatureto warm to ambient temperature
5. extractionThe mixture is extracted with methyl t-butyl ether (4×300 mL)
6. washThe combined organic layers are washed with brine (700 mL)
7. dry with materialdried over anhydrous sodium sulfate (150 g)
8. customThe drying agent is removed by filtration
9. customthe solvents are removed in vacuo

ORD record

ord-8d29ac9e40174f31995ddaf70e9ea9be

Source dataset

uspto-grants-1998_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05840898