Sodium Carbonate → Methyl 3-(benzyloxy)-2',4'-difluorobiphenyl-4-carboxylate

HRID 2272479Notes

Reaction equation

HRID 2272479 reaction equation
[OH:1][C:2]1[CH:11]=[C:10](I)[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[F:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2CCCCC2)[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[C:43]2C(OC)=CC=CC=2OC)CCCCC1>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH2:43]([O:1][C:2]1[CH:11]=[C:10]([C:17]2[CH:16]=[CH:15][C:14]([F:13])=[CH:19][C:18]=2[F:20])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5])[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:37]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 27343342,4-Difluorophenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 11380407Methyl 4-iodosalicylate

Product 1

HCID 117992142Methyl 3-(benzyloxy)-2',4'-difluorobiphenyl-4-carboxylateYield 725.6%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of methyl 2-hydroxy-4-iodobenzoate (22 g), 2,4-difluorophenylboronic acid (25 g), a 2 M aqueous sodium carbonate solution (119 mL), tris(dibenzylideneacetone)dipalladium(0) (5.07 g), and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (4.87 g) in toluene (150 mL) was stirred at 100 C for 2 hours. The reaction mixture was poured to water, and the mixture was filtered through celite. Then, the filtrate was subjected to extraction with ethyl acetate. The obtained organic layer was washed with saturated saline and passed through a basic silica gel, and the solvent was distilled off under reduced pressure. Benzyl bromide (10.4 mL) was added at room temperature to a mixture of the obtained residue, potassium carbonate (21.9 g), and DMF (100 mL), and the mixture was stirred at 70 C for 1 hour in a nitrogen atmosphere. Water was added to the reaction mixture at room temperature, followed by extraction with ethyl acetate. The obtained organic layer was washed with water and saturated saline in this order and dried over anhydrous magnesium sulfate, and then, 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 (30.5 g)

Workup

  1. filtrationthe mixture was filtered through celite
  2. extractionThen, the filtrate was subjected to extraction with ethyl acetate
  3. washThe obtained organic layer was washed with saturated saline
  4. distillationthe solvent was distilled off under reduced pressure
  5. additionBenzyl bromide (10.4 mL) was added at room temperature to a mixture of the obtained residue, potassium carbonate (21.9 g), and DMF (100 mL)
  6. additionWater was added to the reaction mixture at room temperature
  7. extractionfollowed by extraction with ethyl acetate
  8. washThe obtained organic layer was washed with water and saturated saline in this order
  9. dry with materialdried over anhydrous magnesium sulfate
  10. distillationthe solvent was distilled off under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-3ab2b981c0324d22b0dba7073bf24be7
Source dataset
uspto-grants-2015_09
Patent number
US09120777B2

Reaction notes

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