Hydrochloric Acid → 4-(3',4'-Difluoro-4-methylbiphenyl-3-yl)-2,2,6,6-tetramethylpyran-3,5-dione

HRID 1470849Notes

Reaction equation

HRID 1470849 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]([CH3:20])=[C:6]([CH:8]2[C:13](=[O:14])[C:12]([CH3:16])([CH3:15])[O:11][C:10]([CH3:18])([CH3:17])[C:9]2=[O:19])[CH:7]=1.[F:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][C:27]=1[F:28].P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl>C(OCC)(=O)C.CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:21][C:22]1[CH:23]=[C:24]([C:2]2[CH:3]=[CH:4][C:5]([CH3:20])=[C:6]([CH:8]3[C:9](=[O:19])[C:10]([CH3:18])([CH3:17])[O:11][C:12]([CH3:15])([CH3:16])[C:13]3=[O:14])[CH:7]=2)[CH:25]=[CH:26][C:27]=1[F:28]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, Tribasic2×HCID 27343373,4-Difluorobenzeneboronic acid2×HCID 684861614-(5-Chloro-2-methylphenyl)-2,2,6,6-tetramethylpyran-3,5-dione

Product 1

HCID 684883944-(3',4'-Difluoro-4-methylbiphenyl-3-yl)-2,2,6,6-tetramethylpyran-3,5-dioneYield 75%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

To a microwave vial is added 4-(5-chloro-2-methylphenyl)-2,2,6,6-tetramethyl-pyran-3,5-dione (0.20 g, 0.68 mmol), 3,4-difluoro-phenylboronic acid (0.107 g, 0.68 mmol), potassium phosphate (0.722 g, 3.40 mmol), palladium(II) acetate (1.6 mg, 0.0068 mmol) and sodium S-phos-3′-sulphonate (7.0 mg, 0.0136 mmol). Distilled, degassed water (0.75 ml) is next added (washing-down any solids from the slides of the vial), followed by stirring for 5 minutes and flushing with argon. This mixture is then heated at 160° C. under microwave irradiation for 15 minutes, followed by the addition of extra 3,4-difluorophenylboronic acid (0.107 g, 0.68 mmol) and potassium phosphate (0.144 g, 0.68 mmol), then further heating at 160° C. under microwave irradiation for 15 minutes. After cooling to room temperature the reaction mixture is diluted with ethyl acetate (3 ml) and acidified to pH2 with dilute aqueous hydrochloric acid. The organic phase is separated and the aqueous phase is further extracted with ethyl acetate (3×3 ml). All organics are then combined, filtered through a silica plug and evaporated to give a crude product which is dissolved in N,N-dimethylformamide (2.5 ml) and purified by preparative reverse phase HPLC to afford 4-(3′,4′-difluoro-4-methylbiphenyl-3-yl)-2,2,6,6-tetramethylpyran-3,5-dione (0.190 g) as a white solid.

Workup

  1. distillationDistilled
  2. customdegassed water (0.75 ml)
  3. additionis next added (
  4. washwashing-down any solids from the slides of the vial),
  5. customflushing with argon
  6. temperaturefurther heating at 160° C. under microwave irradiation for 15 minutes
  7. temperatureAfter cooling to room temperature the reaction mixture
  8. customThe organic phase is separated
  9. extractionthe aqueous phase is further extracted with ethyl acetate (3×3 ml)
  10. filtrationfiltered through a silica plug
  11. customevaporated
  12. customto give a crude product which
  13. custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-24ecf056a3b0470282e0362ba32c7359
Source dataset
uspto-grants-2015_04
Patent number
US09006429B2

Reaction notes

Loading…