Dimethylformamide → Methyl 3-{[5-(4-cyano-3-fluorophenyl)-4-methylpyridin-2-yl]oxy}-2,2-dimethylpropanoate

HRID 623883Notes

Reaction equation

CN(C)C=O.Br[C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[C:9]([F:15])[CH:8]=1.[CH3:16][C:17]([CH3:40])([CH2:22][O:23][C:24]1[CH:29]=[C:28]([CH3:30])[C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][N:25]=1)[C:18]([O:20][CH3:21])=[O:19].C(=O)([O-])[O-].[Na+].[Na+]>O.C(OCC)(=O)C>[C:11]([C:10]1[CH:13]=[CH:14][C:7]([C:27]2[C:28]([CH3:30])=[CH:29][C:24]([O:23][CH2:22][C:17]([CH3:16])([CH3:40])[C:18]([O:20][CH3:21])=[O:19])=[N:25][CH:26]=2)=[CH:8][C:9]=1[F:15])#[N:12]

Participants

Conditions

Temperature: 60 °C

Procedure

N,N-dimethylformamide (30 mL) was added to 4-bromo-2-fluorobenzonitrile (2000 mg), methyl 2,2-dimethyl-3-{[4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]oxy}propanoate (4191 mg) and palladium chloride (dppf) methylene chloride complex (408 mg), and after adding 2N aqueous sodium carbonate solution (15 mL) to the mixture, the atmosphere was replaced with nitrogen and the resulting mixture was stirred at 60° C. for 7 hours. Ethyl acetate and water were added to the reaction mixture, and the liquids were separated. The organic layer was separated, washed with a saturated brine, and the residue obtained by concentrating the mixture under reduced pressure was purified by silica gel column chromatography (n-hexane:ethyl acetate=90:10 to 80:20) to obtain methyl 3-{[5-(4-cyano-3-fluorophenyl)-4-methylpyridin-2-yl]oxy}-2,2-dimethylpropanoate (3587 mg).

Workup

customthe liquids were separated
customThe organic layer was separated
washwashed with a saturated brine
customthe residue obtained
concentrationby concentrating the mixture under reduced pressure
customwas purified by silica gel column chromatography (n-hexane:ethyl acetate=90:10 to 80:20)

Sources & evidence

ORD record: ord-628a36554cbc4bc5a32b391257ecc054
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09302996B2

Reaction notes

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