5-Iodouracil 11.245g (47.25mmol) was suspended in POCl3 45mL (10eq.) and N,N-dimethylaniline 12mL (2 eq.) was added into the stirred slurry. (Non-exothermic). The flask was flushed with argon and the mixture was refluxed under Ar blanket on oil bath (120-125C) for 30 minutes. The mixture was cooled to RT and the volatiles were evaporated. The residue was dried on oil pump (with TWO dry ice cold traps, to prevent pump damage). The obtained thick greenish residue was treated with ice/ice water slush (about 150mL) and stirred at RT for 30 min, then placed on ice bath and continued for additional 30 min. The precipitated crude product was collected by filtration, washed with ice water and dried on highvac. This crude material (a gray powder, 12.788g) was dissolved in dichloromethane, applied onto a column of silica (150g) in dichloromethane and eluted with straight dichloromethane. The purified product (12.45g of a light-tan sticky solid) was re-crystallized from a small volume of hexane. The crystals were rinsed with ice-cold hexane and dried on highvac. Y=10.915g (84%) of a yellowish heavy crystalline solid.
1H(CDCl3, 400MHz): 8.851(s, 1H); 13C(CDCl3, 100MHz): 167.14, 165.35, 160.11, 93.21
This procedure is a modification of a prep published in Collections of Czech Chemical Society 29 (1964) 121-9 . The procedure was succesfully performed on 50g scale, twice (with average Y=83%)
The starting material is a known mutagen, the product is an irritant. Avoid skin contact. POCl3 is a very nasty irritant/lung-edema choking agent and it also happens to reacts with ice /water in an unpredictable manner (it sits and waits until the water warms up. That’s when the runaway suddenly happens.) POCl3 waste is best quenched by pouring it slowly into a diluted aqueous NaOH at room temperature.