2-CHLORO-5-FLUOROBENZYL ALCOHOL

Synthesis

The synthesis of 2-chloro-5-fluorobenzyl alcohol proceeded as follows:

Step 1: Compound Z-A-1-a (35g, 0.2 mol) was dissolved in methanol (500mL) and concentrated sulfuric acid (5mL) was added slowly. The reaction solution was stirred under the protection of N 2 at 70C for 18 h. Most of the solvent was spun off, then 200 mL of water was added and extracted with ethyl acetate (3x250 mL), dried and spun dry to obtain the red oily material Z-A-1-b (38 g, 100% yield).

Step 2: Compound Z-A-1-b (38g, 0.2 mol) was dissolved in THF (200mL) and methanol (50mL), sodium borohydride (15.4g, 0.4 mol) was added slowly at 0C, and the reaction was stirred at room temperature for 2h. The disappearance of the reaction material was monitored by TLC, and the reaction solution was cooled down to 0C with the addition of 300mL of water, and was extracted with dichloromethane (3x300mL), the organic phase was washed with saturated sodium bicarbonate (500mL), the organic phase was dried and spun dry to obtain a yellow solid 2-chloro-5-fluorobenzyl alcohol (32g, yield 99%).