Isocyanatocarbonyl chloride → 8-(3,5-difluorophenyl)-7,8-dihydropyrano[3,4-e][1,3]oxazine-2,4(3H,5H)-dione
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:14](=[O:15])[CH2:13][CH2:12][O:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[C:16](Cl)([N:18]=[C:19]=[O:20])=[O:17]>>[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:14]3[O:15][C:19](=[O:20])[NH:18][C:16](=[O:17])[C:13]=3[CH2:12][O:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1Participants
Conditions
- Temperature
- 55 °C
Procedure
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)
Workup
- temperatureThe mixture was cooled to RT
- customPartition between EtOAc and saturated NaHCO3 solution
- extractionExtracted with EtOAc(×3 times)
- washThe combined organic layers was washed with brine
- dry with materialdried over Na2SO4
- concentrationconcentrated
- customThe crude product was purified by column chromatography on silica gel
Sources & evidence
- ORD record
- ord-b1b6b21444f4451ba1c8b554e4774097
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08710061B2
Reaction notes
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