Hydrochloric Acid → 4-(1-Hydroxy-1-methylethyl)-6-(trifluoromethyl)pyridine-2-carboxylic acid

HRID 1426327Notes

Reaction equation

[OH:1][C:2]([C:5]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[N:8]=[C:7]([C:15]#N)[CH:6]=1)([CH3:4])[CH3:3].[OH-:17].[Na+].[OH2:19].Cl>C(O)C>[OH:1][C:2]([C:5]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[N:8]=[C:7]([C:15]([OH:19])=[O:17])[CH:6]=1)([CH3:4])[CH3:3]

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of 4-(1-hydroxy-1-methylethyl)-6-(trifluoromethyl)pyridine-2-carbonitrile (0.088 g, 0.38 mmol, from Step C) in ethanol (4 mL) was added 1.0M sodium hydroxide in water (1.5 mL, 1.5 mmol) and the reaction was heated to 90° C. for 20 minutes. Upon cooling to room temperature, the reaction was acidified by the addition of 1N HCl to achieve pH 5 and the ethanol was removed in vacuo. The remaining aqueous mixture was extracted with ethyl acetate (3×). The combined extracts were dried over sodium sulfate, decanted and concentrated to afford product, used without further purification (80 mg, 84%). 1H NMR (400 MHz, CD3OD) δ 8.43 (d, J=1.6 Hz, 1H), 8.10 (d, J=1.6 Hz, 1H), 1.57 (s, 6H); 19F NMR (376 MHz, CD3OD) 5-69.39 (s); LCMS (M+H)+: 250.1.

Workup

temperatureUpon cooling to room temperature
customthe ethanol was removed in vacuo
extractionThe remaining aqueous mixture was extracted with ethyl acetate (3×)
dry with materialThe combined extracts were dried over sodium sulfate
customdecanted
concentrationconcentrated
customto afford product
customused without further purification (80 mg, 84%)

Sources & evidence

ORD record: ord-116161210fa14a1da1eaf3082028a0de
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933085B2

Reaction notes

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