1,2-Dichloroethane → N-methoxy-N-methyl-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide

HRID 623420Notes

Reaction equation

[F:1][C:2]([F:15])([F:14])[CH2:3][O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][N:6]=1.Cl.[CH3:17][NH:18][O:19][CH3:20].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>CN(C)C(=O)C>[CH3:20][O:19][N:18]([CH3:17])[C:9](=[O:11])[C:8]1[CH:12]=[CH:13][C:5]([O:4][CH2:3][C:2]([F:1])([F:15])[F:14])=[N:6][CH:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 6-(2,2,2-trifluoroethoxy)nicotinic acid (10.4 g, 47.3 mmol, Step-1), N,O-dimethylhydroxylamine hydrochloride (5.08 g, 52.1 mmol), HOBT (9.59 g, 71.0 mmol), EDC (13.6 g, 71.0 mmol) and triethylamine (26.4 mL, 189 mmol) in N,N-dimethylacetamide (237 mL) is stirred at 60° C. for 16 hours. The reaction mixture is poured into saturated aqueous sodium hydrogen carbonate (300 mL) and extracted with ethyl acetate (500 mL). The organic layer is washed with saturated aqueous sodium hydrogen carbonate (300 mL×2) 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 6.54 g (52% yield) of the title compound as colorless oil.

Workup

extractionextracted with ethyl acetate (500 mL)
washThe organic layer is washed with saturated aqueous sodium hydrogen carbonate (300 mL×2)
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-400ed5ea2a0a4c039a739e947effe719
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09302991B2

Reaction notes

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