Cesium carbonate → 3-[[3,3-Difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-pyridine-4-carboxylic acid methyl ester

HRID 925268

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]=[CH:7][C:6]=1Cl)=[O:4].C(=O)([O-])[O-].[Cs+].[Cs+].[F:18][C:19]([F:30])([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)[CH2:20][CH2:21][SH:22]>CN(C=O)C.O>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]=[CH:7][C:6]=1[S:22][CH2:21][CH2:20][C:19]([F:30])([F:18])[C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)=[O:4]

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of 3-chloro-pyridine-4-carboxylic acid methyl ester (0.28 g, 1.65 mmol) in DMF (10 ml) are added cesium carbonate (2.68 g, 8.25 mmol) and 3,3-difluoro-3-(4-fluorophenyl)-propane-1-thiol (synthesized according to the methods described in sections a) and b) of example 3) (0.34 g, 1.65 mmol) in a sealed tube. The reaction mixture is stirred at 90° C. for 1 h. After completion of the reaction, the mixture is diluted with water (15 ml) and extracted with EtOAc (3×20 ml). The organic layer is washed with water (20 ml), brine (20 ml), dried over anhydrous sodium sulfate and evaporated to get the crude product, which is purified by column chromatography (silica gel, 10% acetone/hexane) to yield 3-[[3,3-difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-pyridine-4-carboxylic acid methyl ester (0.19 g, 0.56 mmol, 34%).

Workup

customsynthesized
customAfter completion of the reaction
extractionextracted with EtOAc (3×20 ml)
washThe organic layer is washed with water (20 ml), brine (20 ml)
dry with materialdried over anhydrous sodium sulfate
customevaporated
customto get the crude product, which
customis purified by column chromatography (silica gel, 10% acetone/hexane)

Sources & evidence

ORD record: ord-b879061a85c447d7833a3fb4f337e5e4
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09284286B2

Linked notes

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