Acetamide → Methyl 5-acetamido-6-(2,2,2-trifluoroethoxy)nicotinate

HRID 623450Notes

Reaction equation

Cl[C:2]1[C:3]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[C:18]([NH2:21])(=[O:20])[CH3:19].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>C(O)(C)(C)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C.O>[C:18]([NH:21][C:2]1[C:3]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8])(=[O:20])[CH3:19]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of methyl 5-chloro-6-(2,2,2-trifluoroethoxy)nicotinate (3.08 g, 11.4 mmol, Step-1), acetamide (0.70 mL, 13.7 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.73 g, 0.80 mmol), potassium phosphate (7.27 g, 34.3 mmol) and 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (0.34 g, 0.800 mmol) in tert-butyl alcohol (114 mL) is stirred for 3 hours at 110° C. The reaction mixture is poured into water and extricated with ethyl acetate 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 (3:1 to 1:1) to give 0.59 g (18% yield) of the title compound as a white solid.

Workup

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 (3:1 to 1:1)

Sources & evidence

ORD record: ord-a0285588f61546bb85b83ffe530def13
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09302991B2

Reaction notes

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