Ammonia → 2-Chloro-3-methylpyridine-4-carbonitrile

Participants

Reaction Conditions

Reaction Steps

2-Chloro-3-methyl-4-pyridinecarboxylic acid (30 g; 174 mmol) was dissolved in pyridine (250 ml) and cooled to 0° C. Methanesulfonyl chloride (13.6 ml) was then added dropwise and the reaction mixture was stirred at 0° C. for 1 hour. NH3 (gas) was added under pressure and the reaction mixture was stirred at room temperature for 1 h. After the reaction had reached completion, the excess NH3 was removed in vacuo. The reaction mixture was then cooled to 0° C., methanesulfonyl chloride (140 ml) was added and the reaction mixture stirred at room temperature overnight. The mixture was then poured into 0.1 M HCl (200 ml) at 0° C. (with care), and adjusted to pH=7 with 1 M NaOH. The reaction mixture was extracted with EtOAc (2×100 ml), washed with brine, dried (MgSO4), filtered and the solvent evaporated in vacuo. The residue was purified by flash column chromatography over silica gel (Biotage flash purification system; gradient: EtOAc/heptane from 15/85 to 30/70). The product fractions were collected and the solvent was evaporated in vacuo. Yield: 12.6 g of D1.

Provenance & Evidence