Pyridine → 6-Chloro-2-(2,2,2-trifluoro-ethoxy)-nicotinonitrile
Reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=O)=[C:4]([O:11][CH2:12][C:13]([F:16])([F:15])[F:14])[N:3]=1.N1C=CC=CC=1.O=P(Cl)(Cl)Cl.[OH-].[Na+]>C(#N)C.CCOC(C)=O>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]#[N:8])=[C:4]([O:11][CH2:12][C:13]([F:14])([F:16])[F:15])[N:3]=1Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 55 °C
Procedure
To a solution of 6-chloro-2-(2,2,2-trifluoro-ethoxy)-nicotinamide (3, 4.68 g, 18.3 mmol) in acetonitrile (anhydrous, 100 mL) were added pyridine (11.86 mL, 146.8 mmol) and POCl3 (6.72 mL, 73.4 mmol). The reaction was heated at 55° C. for 3 hours. After cooling to room temperature, NaOH solution (10% aq.) was slowly added till pH 9. EtOAc (200 mL) was added and layers separated. The aqueous layer was extracted with EtOAc (2×200 mL). The combined organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The purification was accomplished by silica gel chromatography, eluting with 2%-20% EtOAc/hexanes gradient, to afford 4 g (92% yield) of the titled product.
Workup
- temperatureAfter cooling to room temperature
- customlayers separated
- extractionThe aqueous layer was extracted with EtOAc (2×200 mL)
- dry with materialThe combined organic layer was dried over MgSO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe purification
- washeluting with 2%-20% EtOAc/hexanes gradient
Sources & evidence
- ORD record
- ord-a7041bc3ea7840bd9327e165f1a6c797
- Source dataset
- uspto-grants-2015_04
- Patent number
- US09012431B2
Reaction notes
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