Diazald → 2-Chloro-3-phenylpyridine

Participants

Reaction Steps

A stirred solution of potassium hydroxide (22.6 g, 0.4 mole), ethanol (45.3 mL), and water (36 mL) was treated with N-methyl N-nitroso-p-toluenesulfonamide (22.6 g, 0.1 mole; Aldrich) in ether (204 mL) at 65°. The rate of addition of the solution was regulated by the rate of distillation of the ether diazomethane solution. A diazomethane generation kit containing all polished glass surfaces was used to distill the ethanol diazomethane solution which was received in two collection vessels connected in tandem, the first cooled to 0° and the second to -78°. The combined diazomethane solutions were treated dropwise with the solution of 2-chloronicotinic acid (4.7 g, 0.03 mole) in methanol at -15°. The reaction mixture was maintained at -15° for 4 hr and then slowly allowed to equilibrate to room temperature. The solution was concentrated in vacuo to a yellow solid, partitioned between aqueous sodium carbonate and methylene chloride, and the organic layer was isolated, dried (MgSO4), and concentrated in vacuo to yield 5.2 g (approximately 100%) of methyl 2-chloronicotinate (VI) as a crude oil suitable for reaction with piperazine as given below.

Provenance & Evidence