Hydrochloric Acid → 4-((5-Chloro-6-isopropoxypyridin-3-yl)methoxy)-2,5-difluorobenzoic acid

HRID 512041Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][O:10][C:11]2[C:19]([F:20])=[CH:18][C:14]([C:15]([OH:17])=[O:16])=[C:13]([F:21])[CH:12]=2)[CH:5]=[N:6][C:7]=1Cl.[H-].[Na+].[CH:24]([OH:27])([CH3:26])[CH3:25].Cl>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][O:10][C:11]2[C:19]([F:20])=[CH:18][C:14]([C:15]([OH:17])=[O:16])=[C:13]([F:21])[CH:12]=2)[CH:5]=[N:6][C:7]=1[O:27][CH:24]([CH3:26])[CH3:25]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 4-((5,6-dichloropyridin-3-yl)methoxy)-2,5-difluorobenzoic acid (Preparation 14, 210 mg, 0.67 mmol) in THF (5 mL) was added an oil dispersion of NaH (60%, 157 mg, 3.93 mmol) followed by iso-propanol (5 mL) and the reaction mixture was warmed to 80° C. and stirred for 18 hours under a nitrogen atmosphere. Aqueous hydrogen chloride solution (1 M, 20 mL) was added and the mixture extracted with EtOAc (3×30 mL). The combined organics were dried over magnesium sulfate and the solvent was removed in vacuo. The resulting crude was purified by reverse phase chromatography eluting with H2O/MeCN/HCOOH (95/5/0.1 to 5/95/0.1, Biotage™ 40 g C18-silica gel) to yield the title compound (105 mg, 46%).

Workup

extractionthe mixture extracted with EtOAc (3×30 mL)
dry with materialThe combined organics were dried over magnesium sulfate
customthe solvent was removed in vacuo
customThe resulting crude was purified by reverse phase chromatography
washeluting with H2O/MeCN/HCOOH (95/5/0.1 to 5/95/0.1, Biotage™ 40 g C18-silica gel)

Sources & evidence

ORD record: ord-db8f5c53aa5a448294cec6fe5b1f7ed0
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102621B2

Reaction notes

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