Benzoyl chloride, 3-bromo- → HCID 57978152, compound

A suspension of highly active zinc (Rieke zinc) in THF (100 mg/mL, 12.7 mL, 19.4 mmol) was added via a syringe to a solution of 3-bromo-2-cyanopyridine (1.189 g, 6.497 mmol) in anhydrous THF (20 mL) under an atmosphere of argon. The mixture was stirred for four h at room temperature and then at 50° C. for 15 min. The remaining zinc powder was allowed to settle at the bottom of the flask overnight at −20° C. The top solution was transferred to another flask and cooled to −20° C. To this was added a 1 M solution of copper cyanide di(lithium bromide) complex in THF (6.82 mL) and the resulting mixture was stirred for 5 min at −20° C. and for 35 min at 0° C. and then cooled to −30° C. prior to the addition of 3-bromobenzoyl chloride (1.78 g, 8.12 mmol). The mixture was stirred for 6 h during which time the temperature went from −30° C. to 0° C. The reaction was quenched by the addition of saturated ammonium chloride solution and ethyl acetate was added. The phases were separated and the organic phase was washed with 1 M sodium carbonate solution and with brine. The solution was dried over magnesium sulfate and evaporated. Purification by column chromatography using a gradient of increasing concentration of ethyl acetate in heptane (0-50%) gave 1.18 g (63% yield) of the title compound. 1H NMR (CDCl3) δ 8.92 (dd, 1H), 7.98 (dd, 1H), 7.96 (t, 1H), 7.84-7.81 (m, 1H), 7.73-7.70 (m, 1H), 7.68 (dd, 1H), 7.43 (t, 1H); MS (CI) m/z M+ 287, 289.

1. custombottom of the flask overnight
2. customat −20° C
3. customThe top solution was transferred to another flask
4. temperaturecooled to −20° C
5. stirringthe resulting mixture was stirred for 5 min at −20° C. and for 35 min at 0° C.
6. temperaturecooled to −30° C.
7. stirringThe mixture was stirred for 6 h during which time the temperature
8. customwent from −30° C. to 0° C
9. customThe reaction was quenched by the addition of saturated ammonium chloride solution and ethyl acetate
10. additionwas added
11. customThe phases were separated
12. washthe organic phase was washed with 1 M sodium carbonate solution and with brine
13. dry with materialThe solution was dried over magnesium sulfate
14. customevaporated
15. customPurification by column chromatography
16. temperatureof increasing concentration of ethyl acetate in heptane (0-50%)

ORD record

ord-41ccd8f3d9954372817863a24136b176

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07629356B2