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

HRID 531073Notes

Reaction equation

HRID 531073 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.C1(P(C2CCCCC2)[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[C:37]2C(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>[CH2:37]([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:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:31]=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

Conditions

Temperature
70 °C

Procedure

A mixture of methyl 2-hydroxy-4-iodobenzoate (22 g), (2,4-difluorophenyl)boronic acid (25 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 at 100° C. for 2 hours. The reaction mixture was poured to water at room temperature, 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 short silica gel (NH) column, and the solvent was distilled off under reduced pressure. Benzyl bromide (10.4 mL) was added to a mixture of the obtained residue, potassium carbonate (21.9 g), and DMF (100 mL), and the resultant 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 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-664cd382a244465ea4f7db44eedcb9dd
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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