Extracurricular laboratory: Synthetic route of 4-Chloro-2-fluorobenzyl alcohol

At the same time, in my other blogs, there are other synthetic methods of this type of compound,56456-49-6, 4-Chloro-2-fluorobenzyl alcohol, and friends who are interested can also refer to it.

With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.56456-49-6, name is 4-Chloro-2-fluorobenzyl alcohol, molecular formula is C7H6ClFO, molecular weight is 160.5733, as common compound, the synthetic route is as follows.Safety of 4-Chloro-2-fluorobenzyl alcohol

A suspension of (4-chloro-2-fluorophenyl)methanol (3.24 g, 20.1 mmol), 2-chloro-4-iodopyridine (4.40 g, 18.3 mmol), Cs2CO3 (7.76 g, 23.8 mmol), CuI (3.48 g, 18.7 mmol) and 1,10-phenanthroline (659 mg, 3.66 mmol) in toluene (20 mL) was degassed by bubbling N2 through the suspension for 15 min. The suspension was put under N2 and heated at 105 C. for 18 h. The suspension was cooled, 9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added, and the resulting suspension was passed through a plug of SiO2. The resulting solution was concentrated under reduced pressure. Flash chromatography on silica gel (hexanes/(1:1 EtOAc/hexanes), 100:0 to 0:100) afforded a white solid. A suspension of the white solid and NH4OAc (2.66 g, 34.6 mmol) in 1:1 HCO2H/H2O (20 mL) was heated at reflux with stirring for 4 d. The solution was cooled and concentrated under reduced pressure. The resulting residue was made basic with saturated NaHCO3 solution, and the resulting suspension was filtered. The solid was washed with H2O and CH2Cl2, and dried under reduced pressure to afford 1.28 g (28%) of the title compound as a white solid: 1H NMR (300 MHz, DMSO-d6) delta 11.14 (br s, 1H), 7.59 (dd, J=8.1, 8.1 Hz, 1H), 7.52 (dd, J=10.2, 1.8 Hz, 1H), 7.36 (dd, J=8.1, 1.8 Hz, 1H), 7.25 (d, J=7.2 Hz, 1H), 5.89 (d, J=7.2, 2.4 Hz, 1H), 5.83 (d, J=2.4 Hz, 1H), 5.06 (s, 2H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,56456-49-6, 4-Chloro-2-fluorobenzyl alcohol, and friends who are interested can also refer to it.

Reference:
Patent; ALBANY MOLECULAR RESEARCH, INC.; US2011/3738; (2011); A1;,
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts