Methyl 3-bromo-5-(iodomethyl)-4-methylbenzoate → Methyl 3-bromo-5-(3-fluorobenzyl)-4-methylbenzoate

Temperature

-78 °C

To a THF (0.1 M) suspension of CuCN (2 eq.) was added at −78° C. 3-fluorophenyl magnesium bromide (0.5 M solution in THF, 4 eq.) over a period of 5 min. The resulting mixture was stirred at −78° C. for 20 min and then at 0° C. for another 20 min. The now yellow suspension was re-cooled to −78° C. before methyl 3-bromo-5-(iodomethyl)-4-methylbenzoate (1 eq.) from the previous step was added. The resulting mixture was stirred at −78° C. for 20 min, 0° C. for another 20 min and finally at RT for 16 h. The crude reaction mixture was quenched with a 3:1 (v/v) mixture of sat. aq. NH4Cl:conc. NH4OH and then extracted with ether. The combined organic extracts were washed further with water and brine, dried over Na2SO4, filtered and the filtrate concentrated in vacuo. Further purification of the crude product by way of flash chromatography (SiO2, Hex→1:1 (v/v) Hex:EtOAc) afforded the title compound as a colorless oil.

1. additionwas added at −78° C
2. waitat 0° C. for another 20 min
3. additionwas added
4. stirringThe resulting mixture was stirred at −78° C. for 20 min, 0° C. for another 20 min and finally at RT for 16 h
5. customThe crude reaction mixture
6. customwas quenched with a 3:1 (v/v) mixture of sat. aq. NH4Cl
7. extractionNH4OH and then extracted with ether
8. washThe combined organic extracts were washed further with water and brine
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationthe filtrate concentrated in vacuo
12. customFurther purification of the crude product by way of flash chromatography (SiO2, Hex→1:1 (v/v) Hex:EtOAc)

ORD record

ord-f17c96b6487746f8b781c36c75914c6b

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889714B2