Phosphorus oxychloride → 6-Chloropyrimidine-4-carbonyl chloride

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of 6-hydroxypyrimidine-4-carboxylic acid (10.0 g, 71.4 mmol, prepared according to the method described by Daves, G. C.; Baiocchi, F.; Robins, R. K.; Cheng, C. C. in J. Org. Chem. 1961, 26, 2755-2763) and phosphorus pentachloride (58.0 g, 0.27 mol) was treated with phosphorus oxychloride (100 mL, 1.07 mol) and the resultant mixture was refluxed for 16 hours under nitrogen. The excess phosphorus oxychloride was distilled off and the residue was azeotroped three times with toluene and dried in vacuo. The solid product obtained was suspended in dry dichloromethane (100 mL), cooled (0° C.) and treated with dry DMF (2 mL) and oxalyl chloride (7.9 mL, 91 mmol). The resultant mixture was stirred at room temperature for 15 hours and evaporated in vacuo to afford 6-chloropyrimidine-4-carbonyl chloride as a brown liquid, which was used for the next step.

Provenance & Evidence