Hydrochloric Acid → N-(6-Chloro-4-formyl-3-pyridinyl)-2,2-dimethylpropanamide

Participants

Reaction Conditions

Reaction Steps

A three-necked flask, equipped with a thermometer, a magnetic stirrer and a nitrogen inlet, was flushed with nitrogen. The flask was charged with 10.63 g of 2,2-dimethyl-N-(2-chloro-5-pyridinyl)propanamide (50 mmoles) and stoppered with a rubber septum. 100 Ml of THF was added to the flask. The flask was cooled in a liquid N2 /MeOH slush bath and 52.4 ml (110 mmoles) of 2.1M t-butyllithium was slowly added maintaining the temperature ≤75° C. by the rate of addition. The flask was transferred to a dry-ice/isopropanol (IPA) bath and stirred for 1.5 hours when a solution of 10.95 g (150 mmoles) of dimethylformamide in 5 ml of THF was added. The mixture was stirred at -78° C. for 30 minutes, 40 ml of 6N HCl was then added to the flask and the reaction mixture was allowed to warm to room temperature. After stirring for 30 minutes at room temperature, water and ether were added and the organic layer was separated. The aqueous layer was washed twice with ether and the combined organic layers washed with saturated NaCl, dried over MgSO4 and evaporated to leave an oil. The oil was triturated sequentially with water and ether and filtered to remove precipitated solids. The ethereal filtrate was recovered and dried over MgSO4 and the ether evaporated. Chromatography of the oil residue by preparative liquid chromatography (eluting with 20% EtOAc (ethyl acetate)/hexane) gave 3.5 g of the aldehyde (29 % of theoretical) as a pale yellow solid. The solid was recrystallized from hexane to give yellow needles having a melting point of 105°-106.5° C. Carbon, hydrogen, nitrogen and chlorine content calculated for C11H13ClN2O is C, 54.89; H, 5.44; N, 11.64 and Cl, 14.73 percent by weight which compares to that actually found upon analysis of C, 54.79; H, 5.38; N, 11.63; and Cl, 14.74.

Provenance & Evidence