Thionyl Chloride → 2-Fluoropyridine-3-carbonyl chloride

Participants

Reaction Steps

To a solution of 2-fluoropyridine (10 g, 100 mmol) in THF (150 mL) under −78° C. was added an LDA solution (2 M in heptane/THF/ethylbenzene, 60 mL) dropwise. The mixture was stirred at −78° C. for 3 h, then was quenched with a stream of dry CO2. After warming to RT, the mixture was partitioned between EtOAc (100 mL) and H2O (200 mL). The aqueous layer was acidified to pH between 3-4, and extracted with EtOAc. The organic solution was collected and washed with brine and dried over Na2SO4. After removing the solvent in vacuum, 2-fluoropyridine-3-carboxylic acid was obtained as a brown oil. MS: 140 (M−H). Calc'd. for C6H4FNO2−141.10. 2-Fluoropyridine-3-carboxylic acid (7 g) was suspended in SOCl2 (100 mL). After heating under reflux for 2 h, the mixture became homogeneous. Access SOCl2 was removed in vacuo to afford a brown solid as desired compound.

Provenance & Evidence