Isocyanatocarbonyl chloride → 8-(3,5-difluorophenyl)-7,8-dihydropyrano[3,4-e][1,3]oxazine-2,4(3H,5H)-dione

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Reaction Conditions

Reaction Steps

The mixture of 3-(3,5-difluorophenyl)dihydro-2H-pyran-4(3H)-one (Preparation X2) (800 mg, 3.77 mmol) and carbonisocyanatidic chloride (557 mg, 5.28 mmol) was heated in a sealed bottle at 55° C. for 1 h and then at 130° C. for 2 h. The mixture was cooled to RT. Partition between EtOAc and saturated NaHCO3 solution. Extracted with EtOAc(×3 times). The combined organic layers was washed with brine, dried over Na2SO4 and concentrated. The crude product was purified by column chromatography on silica gel to give 8-(3,5-difluorophenyl)-7,8-dihydropyrano[3,4-e][1,3]oxazine-2,4(3H,5H)-dione (230 mg, 0.818 mmol, 21.69% yield). LC-MS (M+H)+=282.0. 1H NMR (500 MHz, CDCl3) δ ppm 8.94 (br, s., 1 H) 6.85-7.01 (m, 2 H) 6.81 (tt, J=8.81, 2.17 Hz, 1 H) 4.70 (d, J=15.56 Hz, 1 H) 4.49 (dd, J=15.56, 2.14 Hz, 1 H) 4.03-4.12 (m, 2 H) 3.68 (br. s., 1 H)

Provenance & Evidence