Phosphorus oxychloride → 7-Chloro-2-(1,1-difluoroethyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine

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Reaction Steps

This intermediate was synthesized by suspending Intermediate 2 in phosphorus oxychloride (ALDRICH, 21.98 ml, 236 mmol) was heating the mixture under reflux for 2 h, the starting material dissolved meanwhile. An aliquot of the reaction was partitioned between NaCO3 10% aq. (1 mL) and DCM (1 mL) and the organic phase was checked by TLC (Hexane/AcOEt 6/4) showing the reaction was complete. The reaction mixture was slowly added to a mixture of water and ice. The solution was neutralized with 10% aq. Na2CO3 (800 mL approx.) and product was extracted with DCM (250 mL). The aqueous layer was further extracted with DCM (2×150 mL) and the combined organic layers were washed with water (200 mL), then with brine (200 mL) and dried over MgSO4. Solvent was removed under reduced pressure. The crude product was purified (silica gel column, eluting with Hexane/AcOEt mixtures from 100:0 to 50:50%) and Intermediate 3 was obtained as a white solid.

Provenance & Evidence