o-Benzylbenzoic acid → Ethanone, 1-[2-(phenylmethyl)phenyl]-

HRID 2293868Notes

Reaction equation

HRID 2293868 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=O.[C:7]1([CH2:13][C:14]2[CH:22]=[CH:21][CH:20]=[CH:19][C:15]=2C(O)=O)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C[Li]>C(Cl)Cl.CCOCC>[C:7]1([CH2:13][C:14]2[CH:15]=[CH:19][CH:20]=[CH:21][C:22]=2[C:1](=[O:5])[CH3:2])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

6

Reactant 3

HCID 11924o-Benzylbenzoic acidHCID 65578Oxalyl chlorideHCID 178418348HCID 178418348, compound

Product 1

HCID 11356276Ethanone, 1-[2-(phenylmethyl)phenyl]-Yield 63%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (4.1 ml, 47 mmol) was added to a solution of 2-(phenylmethyl)benzoic acid (from Aldrich) in methylene chloride (100 ml) over 5 minutes at room temperature. The solution was allowed to stir at room temperature for 2 hours. The solution was concentrated and the resultant orange gum azeotroped with benzene (twice) and placed under high vacuum for 1 hour. In a separate flask, methyl lithium (1.4M in THF, 100 ml, 140 mmol) was added over 10 minutes to a slurry of CuI2 (13.432 gm, 42.3 mmole) in ether (125 ml). The slurry was allowed to stir for 2 minutes. The above-prepared acid chloride in ether (50 ml) at -78° C. was cannulated over 20 minutes into the dimethyl lithiumcuprate solution, which was also cooled to -78° C. The solution stirred for an additional 20 minutes, then was quenched with methanol (30 ml) and warmed to room temperature. The solution was then added to saturated NH4Cl (200 ml), and the aqueous layer was extracted with ether (twice). The organic layers were combined and washed with brine, then dried over MgSO4, filtered and concentrated to afford an orange oil. The crude oil was purified by flash chromatography on Merck silica gel in 5% EtOAc in hexane. The fractions containing the product were combined and concentrated to afford the title compound as a pale yellow solid (3.090 gm, 63%).

Workup

  1. concentrationThe solution was concentrated
  2. customthe resultant orange gum azeotroped with benzene (twice) and
  3. waitplaced under high vacuum for 1 hour
  4. stirringto stir for 2 minutes
  5. temperaturewas also cooled to -78° C
  6. stirringThe solution stirred for an additional 20 minutes
  7. customwas quenched with methanol (30 ml)
  8. temperaturewarmed to room temperature
  9. additionThe solution was then added to saturated NH4Cl (200 ml)
  10. extractionthe aqueous layer was extracted with ether (twice)
  11. washwashed with brine
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customto afford an orange oil
  16. customThe crude oil was purified by flash chromatography on Merck silica gel in 5% EtOAc in hexane
  17. additionThe fractions containing the product
  18. concentrationconcentrated

Sources & evidence

ORD record
ord-8f5b756318174a3c950665d3a8b7dd9a
Source dataset
uspto-grants-1997_11
Patent number
US05686433

Reaction notes

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