Sodium Chloride → (R)-2-chloro-N-[1-[(3-chloro-2-thienyl)methyl]propyl]-3-nitro-4-pyridinamine

Participants

Reaction Conditions

Reaction Steps

A toluene solution of (R)-N-[1-[(3-chloro-2-thienyl)methyl]propyl]-2-hydroxy-3-nitro4-pyridinamine (Compound IV) (0.1 mole in 100 mL of toluene) containing 2 equivalents of DIPEA hydrochloride is heated to 60° C. and 20.6 grams of phosphorous oxychloride is added over 10 minutes with stirring. The reaction is stirred at 60° C. until complete (3 hours). After cooling to 0° C., 245 grams of 2N sodium chloride is added at such a rate so as to maintain the reaction temperature below 10° C. The biphasic mixture is stirred 1-2 hours at 0° C. before it is allowed to warm to room temperature overnight. The bottom aqueous layer is separated from the organic layer. The organic layer is concentrated in vacuo and the residue purified by flash chromatography, eluting with 25:75 ethyl acetate:heptane, to give Compound V. MS (EI), m/z 345 (10%). 1HNMR (500 Mhz, CDCl3/CD3OD) δ 1.0 (3H, t); 1.5-1.8 (2H, m); 2.9-3.2 (2H, m); 3.8 (1H, m); 6.5 (1H, bd); 6.6 (1H, d ); 7.15 (1H, d); 7.9 (1H, d).

Provenance & Evidence