1,4-Dioxane → 3-(2-Bromo-acetyl)-6-fluoro-2-methyl-benzonitrile

Temperature

100 °C

Degassed Reactant Sn reagent (200 ml, 591 mmol) was added to a stirred mixture of 3-Bromo-6-fluoro-2-methylbenzonitrile (115 g, 537 mmol) and PdCl2(PPh3)2 (18.86 g, 26.9 mmol) in dioxane (1149 ml) at RT, then degassed with N2 and the mixture was stirred at 100° C. for 22 hours. The reaction was cooled to 0° C. and THF (575 mL) and water (230 mL) were added followed by NBS (110 g, 618 mmol) added portionwise over 15 min. After 30 minutes, HPLC showed full consumption of the intermediate ketone. The solution was diluted with MTBE (1000 mL) and washed with 0.5% aqueous HBr (3×500 mL), then washed with water. The organic layers were dried over Na2SO4, filtered and concentrated. A precipitate generated. The solid was filtered and washed several times with hexanes to give the title product.

1. customdegassed with N2
2. temperatureThe reaction was cooled to 0° C.
3. additionTHF (575 mL) and water (230 mL) were added
4. additionadded portionwise over 15 min
5. waitAfter 30 minutes
6. customconsumption of the intermediate ketone
7. additionThe solution was diluted with MTBE (1000 mL)
8. washwashed with 0.5% aqueous HBr (3×500 mL)
9. washwashed with water
10. dry with materialThe organic layers were dried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated
13. filtrationThe solid was filtered
14. washwashed several times with hexanes

ORD record

ord-feb89705245f4e3c9dc66084c443bd1a

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08999990B2