Sodium Carbonate → Ethyl 2-cyclopropyl-6-ethoxy-4'-fluorobiphenyl-4-carboxylate

HRID 530977Notes

Reaction equation

HRID 530977 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[C:8]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:7]=[C:6](OS(C(F)(F)F)(=O)=O)[C:5]=1[C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)[CH3:2].[CH:30]1(B(O)O)[CH2:32][CH2:31]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>[CH:30]1([C:6]2[CH:7]=[C:8]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:9]=[C:4]([O:3][CH2:1][CH3:2])[C:5]=2[C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)[CH2:32][CH2:31]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 2760897Cyclopropylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 117992433Ethyl 2-ethoxy-4'-fluoro-6-(((trifluoromethyl)sulfonyl)oxy)biphenyl-4-carboxylate

Product 1

HCID 90423848Ethyl 2-cyclopropyl-6-ethoxy-4'-fluorobiphenyl-4-carboxylateYield 89.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of ethyl 2-ethoxy-4′-fluoro-6-(((trifluoromethyl)sulfonyl)oxy)biphenyl-4-carboxylate (15.6 g), cyclopropylboronic acid (7.67 g), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (2.20 g), a 2 M aqueous sodium carbonate solution (53.6 mL), tris(dibenzylideneacetone)dipalladium(0) (2.29 g), and toluene (60 mL) was stirred at 100° C. for 2 hours in an argon atmosphere. The reaction mixture was allowed to cool to room temperature and then poured to water, followed by extraction with ethyl acetate. The obtained organic layer was washed with saturated saline 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 (10.5 g).

Workup

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

Sources & evidence

ORD record
ord-2a06ec2ca4b240edb06ada16407d1590
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

Loading…