Dichloromethane → 3-{2-Methyl-4-[3-methyl-5-(2-pyridin-3-yl-4-trifluoromethyl-phenoxy)-phenoxy]-phenyl}-propionic acid ethyl ester

HRID 1822286Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:34])[CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][C:14]2[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([O:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][C:23]=3Br)[CH:15]=2)=[CH:9][C:8]=1[CH3:33])[CH3:2].[N:35]1[CH:40]=[CH:39][CH:38]=[C:37](B(O)O)[CH:36]=1.[F-].[Cs+].C(Cl)Cl>C(#N)C>[CH2:1]([O:3][C:4](=[O:34])[CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][C:14]2[CH:15]=[C:16]([O:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][C:23]=3[C:37]3[CH:36]=[N:35][CH:40]=[CH:39][CH:38]=3)[CH:17]=[C:18]([CH3:20])[CH:19]=2)=[CH:9][C:8]=1[CH3:33])[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 3-{4-[3-(2-bromo-4-trifluoromethyl-phenoxy)-5-methyl-phenoxy]-2-methyl-phenyl}-propionic acid ethyl ester (0.112 g, 0.209 mmol), pyridine-3-boronic acid (0.077 g, 0.626 mmol), and cesium fluoride (0.111 g, 0.731 mmol) in dry ACN (7 mL) is purged with N2 and then treated with 1,1′-bis(diphenylphophino)-ferrocene palladium (II) chloride complex with DCM (0.031 g, 0.042 mmol). The mixture is heated to 100° C. and stirred for 5 hours under N2. The reaction is cooled, and the crude mixture is absorbed on silica gel and purified by flash chromatography using 2/1 hexanes/ethyl acetate to afford 0.089 g (79%) of the title compound. Rf=0.33 (1/1 hexanes/EtOAc). 1H NMR (400 MHz, CDCl3); MS (ES+) m/z mass calculated for C31H28O4NF3 535, found 536 (M+1, 100%).

Workup

customis purged with N2
temperatureThe reaction is cooled
customthe crude mixture is absorbed on silica gel
custompurified by flash chromatography

Sources & evidence

ORD record: ord-00517484518140878e4e4c9438c5decc
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07608639B2

Reaction notes

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