Hydrochloric Acid → 2-(2,6-Difluorophenyl)-1,3-thiazole-4-carboxylic acid

HRID 1499398Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[S:10][CH:11]=[C:12]([C:14]([O:16]CC)=[O:15])[N:13]=1.O.[OH-].[Li+].O.Cl>C1COCC1.CCOC(C)=O>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[S:10][CH:11]=[C:12]([C:14]([OH:16])=[O:15])[N:13]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of ethyl 2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxylate (1.72 g, 6.39 mmol) in THF (40.0 mL), lithium hydroxide monohydrate (1.51 g, 36.0 mmol) was added followed by water (10.0 mL). The mixture was stirred at 60° C. for 5 h. The reaction mixture was then cooled to 0° C., and 6 M HCl was added slowly until the pH reached 2. The mixture was diluted with EtOAc (250 mL), washed with brine (200 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (0-30% MeOH in DCM) to give the title compound as a white solid (1.49 g, 97%). LCMS calc. for C10H6F2NO2S (M+H)+: m/z=242.0. found 242.0.

Workup

temperatureThe reaction mixture was then cooled to 0° C.
washwashed with brine (200 mL)
dry with materialdried over Na2SO4
concentrationconcentrated under reduced pressure
customThe residue was purified by chromatography on silica gel (0-30% MeOH in DCM)

Sources & evidence

ORD record: ord-dc65b94ad5044a7a85a3b48935611600
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09200004B2

Reaction notes

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