Ethanol → 5-(3,3-Difluoroazetidin-1-yl)-4-(2,2,2-trifluoroethoxy)picolinic acid

HRID 1480288Notes

Reaction equation

[F:1][C:2]1([F:20])[CH2:5][N:4]([C:6]2[C:7]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])=[CH:8]C(C#N)=[N:10][CH:11]=2)[CH2:3]1.[OH-:21].[K+].[CH3:23][CH2:24][OH:25]>C(OCC)(=O)C>[F:1][C:2]1([F:20])[CH2:5][N:4]([C:6]2[C:7]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])=[CH:8][C:23]([C:24]([OH:21])=[O:25])=[N:10][CH:11]=2)[CH2:3]1

Participants

Conditions

Temperature: 105 °C

Procedure

To a solution of 5-(3,3-difluoroazetidin-1-yl)-4-(2,2,2-trifluoroethoxy)pyridine-2-carbonitrile (example 223a, 680 mg, 2.32 mmol) in EtOH (8 ml) in a schlenk tube was added a 4M aqueous solution of potassium hydroxide (651 mg, 11.6 mmol). The reaction mixture was stirred at 105° C. for 2 hours. The reaction mixture was diluted with ethyl acetate and poured in a separatory funnel. The organic phase was extracted with a 1M aqueous solution of hydrochloric acid. The organic phase was collected and the aqueous phase was back-extracted with ethyl acetate. Combined organic phases were dried over sodium sulfate and evaporated down to dryness to yield the title compound (397 mg, 55%) as a crude solid which was used without any purification. MS (ESI, m/z): 311.2 (M−H+).

Workup

additionpoured in a separatory funnel
extractionThe organic phase was extracted with a 1M aqueous solution of hydrochloric acid
customThe organic phase was collected
extractionthe aqueous phase was back-extracted with ethyl acetate
dry with materialCombined organic phases were dried over sodium sulfate
customevaporated down to dryness

Sources & evidence

ORD record: ord-e9ca24f14cdb4fedb64964d2b06317f0
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409866B2

Reaction notes

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