Hydrochloric Acid → 2-Hydroxy-6-(trifluoromethyl)nicotinamide

HRID 658353Notes

Reaction equation

C[O-].[Na+].[CH2:4]([C:8]([NH2:10])=[O:9])[C:5]([NH2:7])=[O:6].C(O[CH:14]=[CH:15][C:16](=O)[C:17]([F:20])([F:19])[F:18])C.Cl>CO>[O:6]=[C:5]1[C:4]([C:8]([NH2:10])=[O:9])=[CH:14][CH:15]=[C:16]([C:17]([F:20])([F:19])[F:18])[NH:7]1

Participants

Conditions

Temperature: 45 °C

Procedure

Sodium methoxide (74 g, 1.37 mol) was dissolved in methanol (1,000 mL), and malon diamide (100 g, 0.979 mol) was added to this solution at room temperature. To this mixture, 4-ethoxy-1,1,1-trifluoro-3-buten-2-one (191 g, 1.14 mol) was added dropwise at a temperature between 25 and 30° C., and the resultant mixture was refluxed under heating for 2 hours. After cooling to 45° C., concentrated hydrochloric acid was added to the mixed solution to give a pH of 3 to 4, and 500 mL of methanol was distilled off at normal pressure. To the residue, water (500 mL) was added, and the mixture was stirred for a day at room temperature. The resultant product was precipitated while cooling with ice. Thus obtained crystal was collected by filtration, washed with water, and then dried under reduced pressure, to obtain 167 g of a subject compound (yield: 83%).

Workup

temperatureunder heating for 2 hours
distillationwas distilled off at normal pressure
additionTo the residue, water (500 mL) was added
customThe resultant product was precipitated
temperaturewhile cooling with ice
filtrationThus obtained crystal was collected by filtration
washwashed with water
customdried under reduced pressure

Sources & evidence

ORD record: ord-34c2b56aba994822b4ca63e566bea97d
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08076487B2

Reaction notes

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