Vinylene carbonate → 2-(1-(3,5-Dichloropyridin-4-yl)piperidin-4-yl)oxazole
Reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:17])[C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([C:14]([NH2:16])=[O:15])[CH2:10][CH2:9]1.C1(=O)O[CH:21]=[CH:20]O1>O>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:17])[C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[O:15][CH:20]=[CH:21][N:16]=2)[CH2:10][CH2:9]1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 170 °C
Procedure
To a solution of 1-(3,5-dichloropyridin-4-yl)piperidine-4-carboxamide 23 (0.10 g, 0.36 mmol) in polyphosphoric acid (5 mL) at 80° C. was added vinylene carbonate (35 mg, 0.40 mmol). The mixture was heated at 170° C. for 4 hours, cooled to r.t. and poured into water (200 mL). The mixture was extracted with ethyl acetate (3×50 mL) and the combined organic extracts were washed with water (100 mL), a saturated solution of sodium hydrogen carbonate (50 mL), water (50 mL), brine (50 mL), dried (MgSO4) and concentrated under reduced pressure to furnish a colourless oil (12 mg). The crude product was purified by preparative tlc on silica gel (CH2Cl2, MeOH, 10:1 then hexane, EtOAc, 1:1) to furnish the title compound as a white solid (13 mg, 12%), LC-MS (ESI) Rt 2.66 min, m/z 298 (100%, W); m/z (ESI) C13H14Cl2N3O requires 298.0508 found [M+H]+ 298.0507.
Workup
- temperaturecooled to r.t.
- extractionThe mixture was extracted with ethyl acetate (3×50 mL)
- washthe combined organic extracts were washed with water (100 mL)
- dry with materiala saturated solution of sodium hydrogen carbonate (50 mL), water (50 mL), brine (50 mL), dried (MgSO4)
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-0953535b9b67423aa4b7377404bbe702
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08778925B2
Reaction notes
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