Phosphorus oxychloride → HCID 178457490, compound

Participants

Reaction Steps

5-(Benzyloxy)-2-(2-bromobenzyl)-6-oxo-3,6-dihydro-pyrimidine-4-carboxylic acid (68) (1 g, 2.41 mmol, Eq: 1.00) was dissolved in pyridine (20 ml) and N-(2-(tert-butyldimethylsilyloxy)ethyl)propan-2-amine (8b) (576 mg, 2.65 mmol, Eq: 1.1) was added. Precipitate formed and gave a thick slurry. Additional 5 ml of pyridine were added to ease stirring. The suspension was cooled in an ice/NaCl bath. POCl3 (1.11 g, 673 μl, 7.22 mmol, Eq: 3) was added dropwise, keeping the inside temperature below 0° C. After the addition was complete the mixture was stirred for 45 minutes at 0° C. The reaction was quenched with ice and the organic solvent was mostly removed. The remaining aqueous layer was extracted three times with ethyl acetate. The organic layers were washed with brine, combined, dried over Na2SO4, filtered and concentrated. The remaining oil was taken up in a little dichloromethane, was filtered through Celite and then purified by SiO2 flash chromatography (80 g SiO2, hexanes/ethyl acetate 0-50% ethyl acetate) to afford 5-benzyloxy-2-(2-bromobenzyl)-6-oxo-3,6-dihydro-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropylamide (69) (0.758 g, 1.23 mmol, 51.2% yield) as a light brown oil.

Provenance & Evidence