Dimethylformamide → 3-Chloro-3-(2-chloropyridin-3-yl)acrylonitrile
Reaction equation
O=P(Cl)(Cl)Cl.[Cl:6][C:7]1[C:12]([C:13](=O)[CH3:14])=[CH:11][CH:10]=[CH:9][N:8]=1.[ClH:16].NO.C[N:20]([CH3:23])C=O>>[Cl:16][C:13]([C:12]1[C:7]([Cl:6])=[N:8][CH:9]=[CH:10][CH:11]=1)=[CH:14][C:23]#[N:20]Participants
Conditions
- Temperature
- 0 °C
Procedure
100 ml of dimethyl formamide (DMF) were cooled to 0° C. and POCl3 (35.47 g, 231 mmol, 3 eq.) added dropwise. The reaction was stirred 30 min at 0° C. and a solution of 2-chloro-3-acetyl-pyridine (12 g, 77.12 mmol, 1 eq.) in 15 ml of dimethyl formamide (DMF) was added. Once all added the reaction was warmed to 50° C. and stirred for 8 h. The mixture was cooled to 0° C. and hydroxylamine hydrochloride (21.43 g, 308 mmol, 4 eq.) was added by portions very carefully (exothermic). Once all added the reaction was stirred at room temperature for 2 h and quenched with water. The medium was basified until pH 2-3 was reached with 1N aqueous NaOH and extracted with ethylacetate. The organic layer was washed with brine and dried over MgSO4. Removal of all volatiles under reduced pressure afforded 3-chloro-3-(2-chloropyridin-3-yl)acrylonitrile (13.21 g, 81% yield) as a mixture of isomers which was used without further purification.
Workup
- additionOnce all added the reaction
- temperaturewas warmed to 50° C.
- stirringstirred for 8 h
- temperatureThe mixture was cooled to 0° C.
- additionOnce all added the reaction
- stirringwas stirred at room temperature for 2 h
- customquenched with water
- extractionextracted with ethylacetate
- washThe organic layer was washed with brine
- dry with materialdried over MgSO4
- customRemoval of all volatiles under reduced pressure
Sources & evidence
- ORD record
- ord-20b6f85706724f538823dbfda5b58532
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08476197B2
Reaction notes
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