5-Chloropyrazinoic acid → 5-(2,2-Difluoroethoxy)pyrazine-2-carboxylic acid
Reaction equation
CC(C)([O-:4])C.[K+].Cl[C:8]1[N:9]=[CH:10][C:11]([C:14]([OH:16])=[O:15])=[N:12][CH:13]=1.[F:17][C:18]([F:21])(O)[CH3:19]>CN(C=O)C>[F:17][CH:18]([F:21])[CH2:19][O:4][C:8]1[N:9]=[CH:10][C:11]([C:14]([OH:16])=[O:15])=[N:12][CH:13]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 100 °C
Procedure
Potassium tert-butoxide (4.25 g, 37.84 mmol) is added to a solution of 5-chloropyrazine-2-carboxylic acid (1.00 g, 6.31 mmol) and difluoroethanol (2.59 g, 31.54 mmol) in DMF (20 mL) and the mixture is heated at 100° C. for 2 hours. The reaction is cooled to room temperature and stirred overnight under nitrogen. The reaction is quenched with 1 M HCl (30 mL) and extracted with ethyl acetate (3 times). The combined organic layers are dried over sodium sulfate, filtered, and concentrated to give the crude product. The crude product is purified by silica gel flash chromatography, eluting with a gradient of 0.5% to 10% methanol in dichloromethane and azeotroped with xylenes to remove residual DMF to give the title product (1.18 g, 91%). ES/MS (m/e): 205.0 (M+1).
Workup
- temperatureThe reaction is cooled to room temperature
- customThe reaction is quenched with 1 M HCl (30 mL)
- extractionextracted with ethyl acetate (3 times)
- dry with materialThe combined organic layers are dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customto give the crude product
- customThe crude product is purified by silica gel flash chromatography
- washeluting with a gradient of 0.5% to 10% methanol in dichloromethane
- customazeotroped with xylenes
- customto remove residual DMF
Sources & evidence
- ORD record
- ord-b5365b66e15d4b67834ec9f69189362d
- Source dataset
- uspto-grants-2015_10
- Patent number
- US09169271B2
Reaction notes
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