Benzene, 1-iodo-4-(trifluoromethyl)- → HCID 87232381, compound

HRID 558600Notes

Reaction equation

HRID 558600 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.C([Mg]Cl)(C)C.Br[C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[O:21][C:20](=[O:28])[CH:19]=1>C1COCC1.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:27][C:24]([F:25])([F:26])[C:22]1[O:21][C:20](=[O:28])[CH:19]=[C:18]([C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=2)[CH:23]=1

Participants

7

Reactant 3

HCID 67993Benzene, 1-iodo-4-(trifluoromethyl)-HCID 67001156HCID 67001156, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 87232381HCID 87232381, compoundYield 100.6%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of commercially available 4-iodobenzotrifluoride (1.36 g, 5.00 mmol) in THF (13 mL) at −78° C. was added isopropylmagnesium chloride (2M in THF, 2.63 mL, 5.25 mmol) within 2 min keeping the internal temperature below −65° C., stirring was continued at −78 to −20° C. for 60 min. ZnCl2 (1M in THF, 5.50 mL, 5.50 mmol) was added, the cooling bath was removed, the mixture was allowed to reach 23° C. and stirred at 23° C. for 35 min. Pd(PPh3)4 (58 mg, 1 mol %) and 4-bromo-6-trifluoromethyl-pyran-2-one (example C.22 step 3) (1.22 g, 5.00 mmol) were added at 23° C. and stirring was continued at 23° C. for 30 min [slightly exothermic reaction; internal temperature rose to 45° C.]. Poured into ice cold 0.5 M HCl, extracted with EtOAc, washed with sat. NaHCO3-sol. and brine, dried over Na2SO4, evaporated and dried at HV to give an orange solid (1.55 g), which was purified by MPLC to give the title compound as a yellow solid (1.27 g, 82%). MS (EI) [(M)+]; mp 52° C.

Workup

  1. customthe internal temperature below −65° C.
  2. customthe cooling bath was removed
  3. customto reach 23° C.
  4. stirringstirred at 23° C. for 35 min
  5. customwere added at 23° C.
  6. stirringstirring
  7. waitwas continued at 23° C. for 30 min
  8. custom[slightly exothermic reaction
  9. customrose to 45° C.
  10. extractionextracted with EtOAc
  11. washwashed with sat. NaHCO3-sol
  12. dry with materialand brine, dried over Na2SO4
  13. customevaporated
  14. customdried at HV

Sources & evidence

ORD record
ord-23aa7299ea8c421ab14a6a399797522f
Source dataset
uspto-grants-2011_11
Patent number
US08063048B2

Reaction notes

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