Hydrochloric Acid → 5-Methyl-6-((2,2,2-trifluoroethyl)amino)nicotinic acid
Reaction equation
F[C:2]1[C:11]([CH3:12])=[CH:10][C:5]([C:6]([O:8]C)=[O:7])=[CH:4][N:3]=1.[F:13][C:14]([F:18])([F:17])[CH2:15][NH2:16].Cl>CN1CCCC1=O.CO.[OH-].[Na+]>[CH3:12][C:11]1[C:2]([NH:16][CH2:15][C:14]([F:18])([F:17])[F:13])=[N:3][CH:4]=[C:5]([CH:10]=1)[C:6]([OH:8])=[O:7]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 220 °C
Procedure
A mixture of methyl 6-fluoro-5-methylnicotinate (2.00 g, 11.8 mmol, Step-1 of Amine-36) and 2,2,2-trifluoroethanamine (9.37 g, 95 mmol) in N-methylpyrrolidone (24 mL) is stirred at 220° C. for 2.5 hours under microwave irradiation. The mixture is diluted with MeOH (30 mL), and 2 M aqueous sodium hydroxide solution (15 mL) is added to the mixture. After stirring at 50° C. for 1 hour, the mixture is acidified by 2 M hydrochloric acid, and extracted with EtOAc/hexane (100 mL×3). The combined organic layer is washed with water (100 mL), and dried over sodium sulfate. After filtration, the filtrate is concentrated in vacuo. The residue is crystallized from diisopropyl ether to give 884 mg (32%) of the title compound as a pale pink solid.
Workup
- additionis added to the mixture
- stirringAfter stirring at 50° C. for 1 hour
- extractionextracted with EtOAc/hexane (100 mL×3)
- washThe combined organic layer is washed with water (100 mL)
- dry with materialdried over sodium sulfate
- filtrationAfter filtration
- concentrationthe filtrate is concentrated in vacuo
- customThe residue is crystallized from diisopropyl ether
Sources & evidence
- ORD record
- ord-09c35eb43bf841bbbfdf52a0ad8b0676
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09187475B2
Reaction notes
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