Water → 2-(4-Chlorophenyl)ethyl chloride

Temperature

62.5 °C

To a 4-L, jacketed glass reactor containing a solution of 2-(4-chlorophenyl)ethanol (Compound II) (591 g, 3774 mmol) dissolved in toluene (1250 mL) and N,N-dimethylformamide (41.4 g, 566 mmol) at 60° C. was charged thionyl chloride (302 mL, 4151 mmol) over 30 min. The addition was exothermic with significant gas evolution. The reaction mixture was stirred for 1.5 h at 60 to 65° C. Reaction conversion was monitored by HPLC and 1H NMR. When the amount of 2-(4-chlorophenyl)ethanol remaining was <1 area % by HPLC, the reaction mixture was cooled to 20 to 25° C. Water (1000 mL) was charged to the reactor and the mixture was stirred for 15 min. The aqueous layer was removed and the organic phase was washed twice with saturated sodium bicarbonate solution (1000 mL). Evaporation of the organic phase afforded the title compound as a colorless to yellow oil (641 g, 97% yield, 100 area % by HPLC). 1H NMR (400 Hz, CDCl3) δ 3.06 (t, J=7.2 Hz, 2H), 3.72 (t, J=7.2 Hz, 2H), 7.19 (d, J=10 Hz, 2H), 7.32 (d, J=10 Hz, 2H).

1. additionThe addition
2. customReaction conversion
3. temperaturethe reaction mixture was cooled to 20 to 25° C
4. stirringthe mixture was stirred for 15 min
5. customThe aqueous layer was removed
6. washthe organic phase was washed twice with saturated sodium bicarbonate solution (1000 mL)
7. customEvaporation of the organic phase

ORD record

ord-2bf9a9f962dd483eac2ac2f0d9d8c55e

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952197B2