Sulfuric Acid → alpha-Methyl-4'-(methoxy)[1,1'-biphenyl]-4-acetic acid, ethyl ester

HRID 2380162Notes

Reaction equation

HRID 2380162 reaction equation
[CH3:1]OC1C=CC(C2C=CC(CC(O)=O)=CC=2)=CC=1.S(=O)(=O)(O)O.[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2[CH:37]=[CH:36][C:35]([CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:34][CH:33]=2)=[CH:28][CH:27]=1.C([N-]C(C)C)(C)C.[Li+].CI>O1CCCC1.O.C(O)C>[CH3:1][CH:38]([C:35]1[CH:36]=[CH:37][C:32]([C:29]2[CH:28]=[CH:27][C:26]([O:25][CH3:24])=[CH:31][CH:30]=2)=[CH:33][CH:34]=1)[C:39]([O:41][CH2:42][CH3:43])=[O:40]

Participants

9

Reactant 5

HCID 1118Sulfuric AcidHCID 6328Methyl iodideHCID 13937004-Biphenyl-(4'-methoxy)acetic acidHCID 2724682Lithium diisopropylamideHCID 15733994Ethyl 4-(4-methoxyphenyl)phenylacetate

Product 1

HCID 86746941alpha-Methyl-4'-(methoxy)[1,1'-biphenyl]-4-acetic acid, ethyl esterYield 69.6%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

The known starting material, 4'-methoxy-4-biphenylacetic acid (J. Chem. Soc. 1959, 557) is first converted to its ethyl ester by Fisher esterification with ethanol and concentrated sulfuric acid. To a solution of 4'-methoxy-4-biphenylacetic acid, ethyl ester (30.0 g, 0.110 mol) in tetrahydrofuran (400 mL) at -78° C. is added slowly, 2.01 M lithium diisopropylamide (63 mL). The mixture is stirred for 30 minutes and then methyl iodide (30 mL) is added rapidly. The reaction mixture is warmed to 0° C. for 30 minutes, then at room temperature for 3 hours. The mixture is poured into water (2 L) and is extracted with ethyl acetate (3×1 L). The combined ethyl acetate extract is washed with 1N HCl (1 L), water (1 L) and brine (1 L), dried over MgSO4 and is concentrated under reduced pressure to give 48 g of crude yellow oil. Purification of the product by column chromatography (12% ethyl acetate in hexane) gives 22.0 g (69.6 %) of crystalline material, m.p. 52°-54° C.

Workup

  1. waitat room temperature for 3 hours
  2. extractionis extracted with ethyl acetate (3×1 L)
  3. extractionThe combined ethyl acetate extract
  4. washis washed with 1N HCl (1 L), water (1 L) and brine (1 L)
  5. dry with materialdried over MgSO4
  6. concentrationis concentrated under reduced pressure
  7. customto give 48 g of crude yellow oil
  8. customPurification of the product by column chromatography (12% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-50e66714aa6e4eb3b5c32452b20d0914
Source dataset
uspto-grants-1994_11
Patent number
US05364944

Reaction notes

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