Sodium Carbonate → Methyl 2',4'-difluoro-3-isopropoxybiphenyl-4-carboxylate

HRID 2272486Notes

Reaction equation

HRID 2272486 reaction equation
I[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:12][CH:13]([CH3:15])[CH3:14])[CH:3]=1.[F:16][C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=1B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.C1(C)C=CC=CC=1>[F:16][C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=1[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:12][CH:13]([CH3:15])[CH3:14])[CH:3]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 27343342,4-Difluorophenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 90422834Methyl 4-iodo-2-isopropoxybenzoate

Product 1

HCID 117992133Methyl 2',4'-difluoro-3-isopropoxybiphenyl-4-carboxylateYield 99.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of methyl 4-iodo-2-isopropoxybenzoate (4.10 g), (2,4-difluorophenyl)boronic acid (4.04 g), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.789 g), a 2 M aqueous sodium carbonate solution (19.2 mL), tris(dibenzylideneacetone)dipalladium(0) (0.821 g), and toluene (50 mL) was stirred at 100 C for 2 hours. The reaction mixture was poured to water at room temperature, and the mixture was passed through celite, followed by extraction with ethyl acetate. The obtained organic layer was washed with saturated saline and passed through a short silica gel (NH) column, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (3.90 g)

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe obtained organic layer was washed with saturated saline
  3. distillationthe solvent was distilled off under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-8971a317755b42a5a7bb13f293b54bfa
Source dataset
uspto-grants-2015_09
Patent number
US09120777B2

Reaction notes

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