Cesium fluoride → Methyl 4-(2,4-difluorophenyl)benzoate

HRID 1174951Notes

Reaction equation

HRID 1174951 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1I.[CH3:10][O:11][C:12]([C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1)=[O:13].[F-].[Cs+]>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:10][O:11][C:12]([C:14]1[CH:19]=[CH:18][C:17]([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])=[CH:16][CH:15]=1)=[O:13]

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 1375192,4-Difluoro-1-iodobenzeneHCID 27343694-Methoxycarbonylphenylboronic acid

Product 1

HCID 57771752Methyl 4-(2,4-difluorophenyl)benzoateYield 85.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

Dissolve 2,4-difluoro-1-iodo-benzene (0.25 mL, 2.08 mmol) in anhydrous 1,2-dimethoxyethane (30 mL). Add 4-methoxycarbonyl-phenyl-boronic acid (0.375 g, 2.08 mmol), cesium fluoride (1.58 g, 10.42 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.170 g, 0.208 mmol). Degas the mixture thrice and back-fill with nitrogen. Immerse the mixture into a pre-heated (85° C.) oil bath and stir overnight. Filter the hot mixture through Celite® and concentrate in vacuo. Subject the residue to silica gel flash column chromatography (40 g column, 0-10% ethyl acetate/n-hexane) to yield the desired product (0.441 g, 85%). mass spectrum (n/e): 249.0 (M+1).

Workup

  1. customDegas the mixture thrice
  2. filtrationFilter the hot mixture through Celite®
  3. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-8c19e578ce524d34aacba391684f8cfd
Source dataset
uspto-grants-2010_11
Patent number
US07838543B2

Reaction notes

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