Sodium Cyanide → 4-Fluoro-2-iodophenylacetic acid

Participants

Reaction Steps

To the benzylic bromide 322 (4.90 g, 15.6 mmol) in ethanol (50 mL) was added sodium cyanide (1. 60 g, 32.6 mmol) in water (10 mL) and the mixture was heated to reflux for 3 h. It was then concentrated, partitioned between diethyl ether and water; organic phase was collected, washed with brine, dried (MgSO4), filtered and concentrated to afford crude nitrile 323. To this material in 1:1 THF/methanol (50 mL) was added lithium hydroxide monohydrate (1.75 g, 41.7 mmol), in water (12 mL) and the mixture was heated to reflux for 24 h. It was then cooled, partially concentrated and the aqueous residue was washed with ether, then acidified with 3M HCl (aq) and extracted with ether. The extract was washed with brine, dried (MgSO4), filtered and concentrated to yield acid 324 (3.95 g, 90% yield over two steps). LCMS: (M+Na) 303.0.

Provenance & Evidence