Sodium Carbonate → Methyl 5-(benzyloxy)-2-cyclopropyl-2',4'-difluorobiphenyl-4-carboxylate

HRID 531075Notes

Reaction equation

HRID 531075 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:24]([O:26][CH3:27])=[O:25])=[CH:11][C:12](Br)=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=2[F:22])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:28]1(B(O)O)[CH2:30][CH2:29]1.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>[CH2:1]([O:8][C:9]1[C:10]([C:24]([O:26][CH3:27])=[O:25])=[CH:11][C:12]([CH:28]2[CH2:30][CH2:29]2)=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=2[F:22])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 2760897Cyclopropylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 117992213Methyl 5-(benzyloxy)-2-bromo-2',4'-difluorobiphenyl-4-carboxylate

Product 1

HCID 117992146Methyl 5-(benzyloxy)-2-cyclopropyl-2',4'-difluorobiphenyl-4-carboxylateYield 65%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of methyl 5-(benzyloxy)-2-bromo-2′,4′-difluorobiphenyl-4-carboxylate (34.3 g), cyclopropylboronic acid (17.0 g), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (4.87 g), a 2 M aqueous sodium carbonate solution (119 mL), tris(dibenzylideneacetone)dipalladium(0) (5.07 g), and toluene (150 mL) was stirred overnight at 100° C. The reaction mixture was poured to water at room temperature, 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 (20.3 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-0396acd7dd7045c29b529be38e600c06
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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