Sodium Carbonate → HCID 117992145, compound

HRID 531126Notes

Reaction equation

HRID 531126 reaction equation
[CH:1]1([C:4]2[C:5](OS(C(F)(F)F)(=O)=O)=[CH:6][C:7]([O:14][CH2:15][CH3:16])=[C:8]([CH:13]=2)[C:9]([O:11]C)=O)[CH2:3][CH2:2]1.[F:25][C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH: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:1]1([C:4]2[CH:13]=[C:8]([CH2:9][OH:11])[C:7]([O:14][CH2:15][CH3:16])=[CH:6][C:5]=2[C:30]2[CH:29]=[CH:28][CH:27]=[C:26]([F:25])[CH:31]=2)[CH2:2][CH2:3]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 117992277HCID 117992277, compound

Product 1

HCID 117992145HCID 117992145, compoundYield 92.6%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of methyl 5-cyclopropyl-2-ethoxy-4-(((trifluoromethyl)sulfonyl)oxy)benzoate (2.50 g), (3-fluorophenyl)boronic acid (1.90 g), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.418 g), a 2 M aqueous sodium carbonate solution (10.2 mL), tris(dibenzylideneacetone)dipalladium(0) (435 mg), and toluene (20 mL) was stirred overnight at 100° C. in an argon atmosphere. Water was added to the reaction mixture, and then, the mixture was filtered through celite, followed by extraction with ethyl acetate. The organic layer was 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). A THF (10 mL) solution of the obtained purified product was added to a THF (20 mL) suspension of lithium aluminum hydride (500 mg) under ice cooling in a nitrogen atmosphere. After stirring at the same temperature as above for 30 minutes, water (0.5 mL) and a 15% aqueous sodium hydroxide solution (0.5 mL) were added thereto, and the mixture was stirred for 5 minutes. Water (1.5 mL) was further added to the reaction mixture, and the mixture was stirred for 30 minutes and then filtered. The filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (1.80 g).

Workup

  1. filtrationthe mixture was filtered through celite
  2. extractionfollowed by extraction with ethyl acetate
  3. distillationthe solvent was distilled off under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)
  5. customA THF (10 mL) solution of the obtained purified product
  6. additionwas added to a THF (20 mL) suspension of lithium aluminum hydride (500 mg) under ice cooling in a nitrogen atmosphere
  7. additiona 15% aqueous sodium hydroxide solution (0.5 mL) were added
  8. stirringthe mixture was stirred for 5 minutes
  9. additionWater (1.5 mL) was further added to the reaction mixture
  10. stirringthe mixture was stirred for 30 minutes
  11. filtrationfiltered
  12. concentrationThe filtrate was concentrated under reduced pressure
  13. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-4d89a736aae34dbb8012fc3df3882cc3
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

Loading…