Potassium Phosphate, Tribasic → HCID 86663661, compound

HRID 1193215Notes

Reaction equation

HRID 1193215 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:7]([C:10]([F:13])([F:12])[F:11])=[CH:8][CH:9]=1)[CH:5]=[O:6].[Cl:14][C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C:2]2[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[C:4]([CH:5]=[O:6])[CH:3]=2)=[CH:17][CH:16]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 742994-Chlorophenylboronic acidHCID 177507585-Chloro-2-(trifluoromethyl)benzaldehyde

Product 1

HCID 86663661HCID 86663661, compoundYield 130.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalyst

Procedure

To a mixture of 3-chloro-6-trifluoromethylbenzaldehyde (1.0 g, 4.79 mmol), 4-chlorophenyl boronic acid (1.12 g, 7.19 mmol), potassium phosphate (2.03 g, 9.59 mmol), dicyclohexyl-(2′,6′-dimethoxy-biphenyl-2-yl)-phosphane (0.079 g, 0.19 mmol) and palladium acetate (0.022 g, 0.096 mmol) is added degassed toluene (9 ml), then the mixture is further purged with nitrogen. The suspension is next sealed then stirred at ambient temperature for 5 minutes, than heated at 160° C. for 1 hour under microwave irradiation. After cooling the reaction mixture is partitioned between 2M hydrochloric acid and dichloromethane, and the aqueous phase further extracted with dichloromethane (×2). The organic fractions are combined then evaporated under reduced pressure to yield a crude product which is purified by flash column chromatography (100% hexane to 10% ethyl acetate in hexanes as eluant) to afford 4′-chloro-4-trifluoromethyl-biphenyl-3-carbaldehyde (1.78 g) as an orange gum. This material is used directly in the next step.

Workup

  1. additionis added
  2. customdegassed toluene (9 ml)
  3. customthe mixture is further purged with nitrogen
  4. customnext sealed
  5. temperaturethan heated at 160° C. for 1 hour under microwave irradiation
  6. temperatureAfter cooling the reaction mixture
  7. customis partitioned between 2M hydrochloric acid and dichloromethane
  8. extractionthe aqueous phase further extracted with dichloromethane (×2)
  9. customThe organic fractions are combined then evaporated under reduced pressure
  10. customto yield a crude product which
  11. customis purified by flash column chromatography (100% hexane to 10% ethyl acetate in hexanes as eluant)

Sources & evidence

ORD record
ord-f5bb50374b8845f4997f1047933aae39
Source dataset
uspto-grants-2014_03
Patent number
US08680299B2

Reaction notes

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