Reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.Cl[C:11]1[CH:19]=[CH:18][C:14]([C:15]([NH2:17])=[O:16])=[CH:13][N:12]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CC(N(C)C)=O.O>[CH:6]([C:5]1[CH:8]=[CH:9][C:2]([O:1][C:11]2[CH:19]=[CH:18][C:14]([C:15]([NH2:17])=[O:16])=[CH:13][N:12]=2)=[CH:3][CH:4]=1)=[O:7]Participants
Conditions
- Temperature
- 130 °C
Procedure
Combine 4-hydroxy benzaldehyde (7.201 g, 59.0 mmol), 6-chloronicotinamide (9.605 g, 57.5 mmol), and potassium carbonate (19.86 g, 143.7 mmol) in dimethylacetamide (190 mL). Stir and heat at 130° C. After 18 h, cool to ambient temperature and dilute with water (600 mL). Extract aqueous layer with ethyl acetate (3×500 mL). Wash combined ethyl acetate extracts with water (1×) and brine (1×), successively, dry over anhydrous magnesium sulfate, filter, and concentrate. Purification by silica gel chromatography (1:1 ethyl acetate:hexanes→ethyl acetate) to provide 6.852 g (49%, 90% pure) of the title compound as a white solid: mass spectrum (electrospray): m/z=243.0 (M+1); 1H NMR (methanol-d4): 9.97 (s, 1H), 8.70 (d, 1H, J=2.4 Hz), 8.36 (dd, 1H, J=2.4, 8.8 Hz), 8.06-8.02 (m, 2H), 7.42-7.37 (m, 2H), 7.19 (d, 1H, J=9.3 Hz).
Workup
- temperaturecool to ambient temperature
- washWash
- dry with materialsuccessively, dry over anhydrous magnesium sulfate
- filtrationfilter
- concentrationconcentrate
- customPurification by silica gel chromatography (1:1 ethyl acetate:hexanes→ethyl acetate)
Sources & evidence
- ORD record
- ord-a8794c19e9b842b095e46cf3ced430a0
- Source dataset
- uspto-grants-2008_06
- Patent number
- US07381719B2
Linked notes
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