Formic Acid → 4-[4-[(3E)-1-(4-chloro-2-fluorophenyl)-3-hydroxyimino-3-(2-methyl-4-pyridinyl)propyl]phenyl]thiophene-2-carboxylic acid

HRID 1617610Notes

Reaction equation

C([O:3][C:4]([C:6]1[S:7][CH:8]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([CH:17]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=3[F:36])[CH2:18]/[C:19](=[N:27]\[OH:28])/[C:20]3[CH:25]=[CH:24][N:23]=[C:22]([CH3:26])[CH:21]=3)=[CH:13][CH:12]=2)[CH:10]=1)=[O:5])C.[Li+].[OH-].C(O)=O>O1CCOCC1.O>[Cl:35][C:32]1[CH:33]=[CH:34][C:29]([CH:17]([C:14]2[CH:13]=[CH:12][C:11]([C:9]3[CH:10]=[C:6]([C:4]([OH:5])=[O:3])[S:7][CH:8]=3)=[CH:16][CH:15]=2)[CH2:18]/[C:19](=[N:27]\[OH:28])/[C:20]2[CH:25]=[CH:24][N:23]=[C:22]([CH3:26])[CH:21]=2)=[C:30]([F:36])[CH:31]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 4-{4-[1-(4-chloro-2-fluoro-phenyl)-3-[(E)-hydroxyimino]-3-(2-methyl-pyridin-4-yl)-propyl]-phenyl}-thiophene-2-carboxylic acid ethyl ester (15 mg) in dioxane/water (1.5 mL, 1:1) was added LiOH (7.2 mg) and the reaction mixture heated by microwave irradiation to 100° C. for 30 min. Formic acid was added to neutralize LiOH and the solvent mixture removed by evaporation under reduced pressure. Purification of the crude reaction product by silica column chromatography eluting with a mixture of dichloromethane/methanol (95:5, containing 4% formic acid) provided 14 mg (98%) of the title compound as an off-white powder, MS (ESI+): m/z=495.1 [M+H]+.

Workup

customthe solvent mixture removed by evaporation under reduced pressure
customPurification of the crude
customreaction product by silica column chromatography
washeluting with a mixture of dichloromethane/methanol (95:5, containing 4% formic acid)

Sources & evidence

ORD record: ord-adb77e2479554683b7bd2a20b6c8a17d
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765730B2

Reaction notes

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