Cyproheptadine → [1,1'-Biphenyl]-2,5-dicarboxylic acid, 4'-methyl-, 2,5-dimethyl ester

HRID 1493846Notes

Reaction equation

HRID 1493846 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1.[Li]C(C)(C)C.[CH3:14][O:15][C:16](=[O:28])[C:17]1[CH:26]=[CH:25][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:19][C:18]=1Br.CN1CCC(=C2C3C(=CC=CC=3)C=CC3C2=CC=CC=3)CC1>O1CCCC1.[Cl-].[Cl-].[Zn+2].Cl[Ni](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:14][O:15][C:16](=[O:28])[C:17]1[CH:26]=[CH:25][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:19][C:18]=1[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 2913CyproheptadineHCID 78054-BromotolueneHCID 87741Dimethyl 2-bromoterephthalateHCID 178418306HCID 178418306, compound

Product 1

HCID 105655[1,1'-Biphenyl]-2,5-dicarboxylic acid, 4'-methyl-, 2,5-dimethyl esterYield 85.3%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418751HCID 178418751, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

4-Bromotoluene (6 g) was dissolved in tetrahydrofuran (20 ml). To this solution at -78° C. under N2 was added over a ten minute period, 1.7M tBuLi (42 ml). After two hours at room temperature, the reaction mixture was cooled to 0° C. and 1M ZnCl2 (36 ml) was added over a ten minute period. After one half hour at room temperature, bis(triphenylphosphine)nickel(II) chloride (1.32 g) was added followed by dimethyl-2-bromo-terepthalate (6 g) in tetrahydrofuran (20 ml) dropwise over a five minute period. The reactin mixture was stirred at room temperature for two hours. The tetrahydrofuran was removed under reduced pressure. The residue was treated with ethyl acetate and 1N HCl and the layers separated. The organic phase was washed with water, brine, dried over magnesium sulfate and evaporated gave the crude product. Chromatography on silica gel using 5% hexanes/methylene chloride gave the desired product (5.33 g).

Workup

  1. additionTo this solution at -78° C. under N2 was added over a ten minute period
  2. waitAfter one half hour at room temperature
  3. customThe tetrahydrofuran was removed under reduced pressure
  4. additionThe residue was treated with ethyl acetate and 1N HCl
  5. customthe layers separated
  6. washThe organic phase was washed with water, brine
  7. dry with materialdried over magnesium sulfate
  8. customevaporated
  9. customgave the crude product

Sources & evidence

ORD record
ord-87573bcf06304a439681c3c29cba30af
Source dataset
uspto-grants-1991_06
Patent number
US05025007

Reaction notes

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