Methanol → 4-(4-Chloro-2-fluorophenyl)nicotinic acid

HRID 1398288Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]([O:16]C)=[O:15])=[CH:12][N:11]=[CH:10][CH:9]=2)=[C:4]([F:18])[CH:3]=1.CO.[OH-].[Na+]>O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]([OH:16])=[O:15])=[CH:12][N:11]=[CH:10][CH:9]=2)=[C:4]([F:18])[CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of methyl 4-(4-chloro-2-fluorophenyl)nicotinate (15 g, 56.5 mmol) (as prepared in Ex 1, Part B) in a solvent mixture of methanol (150 mL) and water (150 mL) cooled to 0° C. was added sodium hydroxide (9.03 g, 226 mmol) and the mixture was warmed to room temperature and stirred for 1 h. The reaction mixture was concentrated under reduced pressure and pH of the resultant aqueous solution was adjusted to pH=4 using 1.5 N Hydrochloric acid during which time the product crashed out as a solid. Filtration of the mixture provided 4-(4-chloro-2-fluorophenyl)nicotinic acid (9 g, 35.8 mmol, 63% yield) as an off white solid. LC/MS (ESI) m/e 252.0 [(M+H)+, calcd for C12H8ClFNO2 252.1]; LC/MS retention time (method A): tR=0.97 min.

Workup

temperaturethe mixture was warmed to room temperature
concentrationThe reaction mixture was concentrated under reduced pressure and pH of the resultant aqueous solution
filtrationFiltration of the mixture

Sources & evidence

ORD record: ord-1a5a406f56ef4ec79cd4bbe4d4117485
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901305B2

Reaction notes

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