Hydrochloric Acid → 5-(4-Cyanophenyl)-6-(2,2,2-trifluoroethoxy)nicotinic acid

HRID 240741Notes

Reaction equation

C[O:2][C:3](=[O:24])[C:4]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=2)[C:7]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])=[N:6][CH:5]=1.C1COCC1.[OH-].[Li+].Cl>O>[C:16]([C:13]1[CH:12]=[CH:11][C:10]([C:8]2[C:7]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])=[N:6][CH:5]=[C:4]([CH:9]=2)[C:3]([OH:24])=[O:2])=[CH:15][CH:14]=1)#[N:17]

Participants

Conditions

Temperature: 40 °C

Procedure

In a 25 mL round-bottomed flask, the above prepared 5-(4-cyano-phenyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinic acid methyl ester (0.891 g, 2.65 mmol, Eq: 1.00) was combined with THF (7 mL) and water (3.5 mL) to give a light yellow biphasic system. Lithium hydroxide (127 mg, 5.3 mmol, Eq: 2) was added and the reaction mixture was stirred at 40° C. for 3 hours when TLC indicated the reaction to be complete. Work up: 10 mL H2O and 7 mL HCl 1N were added, the mixture extracted with AcOEt (2×50 mL), the organic layers were combined, washed with brine, dried over Na2SO4 and concentrated in vacuo. Trituration with heptane/EtOAc 9:1 afforded finally 794 mg of the desired title product as a white solid; MS (EI) 321.2 (M−H)−.

Workup

customto give a light yellow biphasic system
customthe reaction
extractionthe mixture extracted with AcOEt (2×50 mL)
washwashed with brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-caec004d50204b06af9afa880e0c8643
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08648099B2

Reaction notes

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