Ethylene Oxide → 2-Chloro-4-fluoro-3-(2-hydroxyethyl)benzonitrile

To a solution of 2-chloro-4-fluorobenzonitrile (20.0 g, 128.6 mmol) in THF (200 mL) added LDA (28% wt in THF, 71.0 mL, 142.0 mmol) at −78° C. After addition, the mixture was stirred at the same temperature for 5 h, then ethylene oxide (9.7 ml, 194.2 mmol) was added. The reaction mixture was allowed to warm to R. T. gradually and stirred overnight. The reaction was quenched by adding saturated aqueous NH4Cl solution and extracted with EtOAc (400 mL). The EtOAc extracts were washed with water, brine and dried over Na2SO4. After the solvent was removed, the residue was purified by SiO2 column to give 2-chloro-4-fluoro-3-(2-hydroxyethyl)benzonitrile (17.0 g, 66%). 1H NMR (400 MHz, CDCl3, δ in ppm) 7.58 (dd, J=5.5, 8.6 Hz, 1H), 7.10 (t, J=8.6 Hz, 1H), 3.88 (m, 2H), 3.13 (t, J=6.8 Hz, 2H).

1. additionAfter addition
2. temperatureto warm to R
3. stirringgradually and stirred overnight
4. customThe reaction was quenched
5. additionby adding saturated aqueous NH4Cl solution
6. extractionextracted with EtOAc (400 mL)
7. washThe EtOAc extracts were washed with water, brine
8. dry with materialdried over Na2SO4
9. customAfter the solvent was removed
10. customthe residue was purified by SiO2 column

ORD record

ord-982c268836524ff3883871b2400c1d5c

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08629167B2