Potassium Carbonate → 4-[[3,3-Difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-2-methyl-thiazole-5-carboxylic acid ethyl ester

HRID 925277Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([CH3:11])=[N:8][C:7]=1[SH:12])=[O:5])[CH3:2].Br[CH2:14][CH2:15][C:16]([C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)([F:18])[F:17].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([CH3:11])=[N:8][C:7]=1[S:12][CH2:14][CH2:15][C:16]([F:18])([F:17])[C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of give 4-mercapto-2-methyl-thiazole-5-carboxylic acid ethyl ester (0.58 g, 2.83 mmol) in acetone (10 ml) are added 1-(3-bromo-1,1-difluoro-propyl)-4-fluoro-benzene (synthesized according to the methods described in sections a) to e) of example 1) (0.72 g, 2.83 mmol) and potassium carbonate (0.78 g, 5.66 mmol) an the mixture is heated at 80° C. for 16 h. Acetone is evaporated, diluted with water (40 ml) and extracted with EtOAc (3×30 ml). The crude product is purified by column chromatography (silica gel, 10% EtOAc/hexane) yielding 4-[[3,3-difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-2-methyl-thiazole-5-carboxylic acid ethyl ester (0.6 g, 1.6 mmol, 56%).

Workup

customsynthesized
customAcetone is evaporated
additiondiluted with water (40 ml)
extractionextracted with EtOAc (3×30 ml)
customThe crude product is purified by column chromatography (silica gel, 10% EtOAc/hexane)

Sources & evidence

ORD record: ord-70b467d4f7d1439c82e361e80e93ca53
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09284286B2

Reaction notes

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