Triethylamine → 5-chloro-N-methoxy-N-methyl-6-(2,2,2-trifluoroethoxy)nicotinamide
Reaction equation
[Cl:1][C:2]1[C:3]([O:11][CH2:12][C:13]([F:16])([F:15])[F:14])=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=O.Cl.[CH3:18][NH:19][O:20][CH3:21].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>ClCCl.O>[Cl:1][C:2]1[C:3]([O:11][CH2:12][C:13]([F:16])([F:15])[F:14])=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([N:19]([O:20][CH3:21])[CH3:18])=[O:9]Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
A mixture of 5-chloro-6-(2,2,2-trifluoroethoxy)nicotinic acid (2.0 g, 7.8 mmol, Step-1), N,O-dimethylhydroxylamine hydrochloride (0.916 g, 9.39 mmol), HBTU (3.56 g, 9.39 mmol) and triethylamine (5.45 mL, 39.1 mmol) in dichloromethane (39 mL) is stirred at room temperature for 3 hours. The reaction mixture is poured into water (100 mL) and extracted with dichloromethane (200 mL). The organic layer is washed with water (100 mL) and dried over sodium sulfate and concentrated in vacuo. The residue is purified by column chromatography on silica gel eluting with n-hexane/ethyl acetate (4:1) to give 2.2 g (94% yield) of the title compound as a white solid.
Workup
- extractionextracted with dichloromethane (200 mL)
- washThe organic layer is washed with water (100 mL)
- dry with materialdried over sodium sulfate
- concentrationconcentrated in vacuo
- customThe residue is purified by column chromatography on silica gel eluting with n-hexane/ethyl acetate (4:1)
Sources & evidence
- ORD record
- ord-9f2b34bc39e241659709a07a049439d1
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09302991B2
Reaction notes
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