Bromine → HCID 86691330, compound

Temperature

0 °C

To a stirred suspension of E-2,6-difluorocinnamic acid (2.0 g, 11 mmol) in dichloromethane at 0° C. is added bromine (0.56 mL, 11 mmol) dropwise. The mixture is stirred overnight as it is slowly allowed to reach temperature. Evaporation of the volatiles under reduced pressure affords the crude dibrominated carboxylic acid intermediate that is directly carried to the next step without further purification. To the crude solid is added DMF (20 mL) and a small crystal of BHT. The mixture is cooled to 0° C., and triethylamine (3 mL) is added. The mixture is stirred overnight as it is slowly allowed to reach temperature. Contents are poured in 2N aqueous HCl, extracted with diethyl ether, and the combined organic fractions are washed with saturated aqueous NaCl. Evaporation of the volatiles yields a crude product that is further purified by passing on a SiO2 plug using pentane as an eluent. Evaporation of the solvents under reduced pressure affords bromoalkene 11q as a colorless oil (1.35 g, 57%, ≧20:1 d.r. by 19F-NMR). 1H-NMR (CDCl3, 300 MHz): δ=7.42-7.32 (m, 1H), 7.07 (d, J=7.9 Hz, 1H), 7.05-6.95 (m, 2H), 6.84 (d, J=7.9 Hz, 1H). 13C-NMR (CDCl3, 75 MHz): δ=159.9 (dd, J=250, 7 Hz), 130.0 (t, J=10 Hz), 122.3, 114.8, 130.0 (t, J=20 Hz), 111.5 (dd, J=18, 7 Hz). 19F-NMR (CDCl3, 282 MHz): δ=−108.5. HR-MS (EI): Calcd. for C8H5F2Br [M+]: 217.9543. found 217.9538.

1. customEvaporation of the volatiles under reduced pressure
2. customaffords the crude dibrominated carboxylic acid intermediate that
3. customis directly carried to the next step without further purification
4. additionTo the crude solid is added DMF (20 mL)
5. additiontriethylamine (3 mL) is added
6. stirringThe mixture is stirred overnight as it
7. additionContents are poured in 2N aqueous HCl
8. extractionextracted with diethyl ether
9. washthe combined organic fractions are washed with saturated aqueous NaCl
10. customEvaporation of the volatiles
11. customyields a crude product that
12. customis further purified
13. customEvaporation of the solvents under reduced pressure

ORD record

ord-796e1764fbfb4bada78658997a41686a

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403781B2