Hydrochloric Acid → HCID 68295566, compound

HRID 572522Notes

Reaction equation

HRID 572522 reaction equation
[CH3:1][C:2]1[CH:24]=[C:23]([CH3:25])[CH:22]=[CH:21][C:3]=1[C:4]([C:6]1[CH:20]=[CH:19][CH:18]=[CH:17][C:7]=1[C:8]([N:10]([CH2:12][C:13]([O:15][CH3:16])=[O:14])[CH3:11])=[O:9])=O.C[O-].[Na+].Cl.CC1C=CC(S(O)(=O)=O)=CC=1>CO.C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:24]=[C:23]([CH3:25])[CH:22]=[CH:21][C:3]=1[C:4]1[C:6]2[C:7](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:8](=[O:9])[N:10]([CH3:11])[C:12]=1[C:13]([O:15][CH3:16])=[O:14]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6101p-Toluenesulfonic acid2×HCID 10942334Sodium MethoxideHCID 68295574HCID 68295574, compound

Product 1

HCID 68295566HCID 68295566, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Procedure

An ice cold mixture of methyl 2-(2-(2,4-dimethylbenzoyl)-N-methylbenzamido)acetate (60 g, 177 mmol) in methanol (400 mL) was treated with sodium methoxide (42.0 g, 194 mmol) and the resultant was allowed to stir at ambient temperature for 1 hour. The mixture was cooled to 0° C., treated with HCl (21.78 mL, 265 mmol) and then concentrated. The residue was dissolved in ethyl acetate, washed with water, brine, dried over Na2SO4, filtered and concentrated. The crude intermediate was treated with Toluene (400 mL) and pTsOH (16.81 g, 88 mmol) and the mixture was heated at 120° C. for 1 hour. Additional pTsOH (16.81 g, 88 mmol) was added and the mixture was stirred at 120° C. overnight. LCMS indicated complete reaction. The mixture was concentrated and the residue was dissolved in ethyl acetate. The organic phase was washed with water, then brine, dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel (0-60% EA on hexane) to give the desired product as a white solid (24 g, 53%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.48-8.57 (m, 1 H) 7.50-7.58 (m, 2 H) 7.10-7.14 (m, 1 H) 7.04 (s, 3 H) 3.61 (s, 3 H) 3.54 (s, 3 H) 2.39 (s, 3 H) 2.04 (s, 3 H); LC/MS (m/z) ES+=322 (M+1).

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. temperaturethe mixture was heated at 120° C. for 1 hour
  9. stirringthe mixture was stirred at 120° C. overnight
  10. customreaction
  11. concentrationThe mixture was concentrated
  12. dissolutionthe residue was dissolved in ethyl acetate
  13. washThe organic phase was washed with water
  14. dry with materialbrine, dried over Na2SO4
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customThe residue was purified on silica gel (0-60% EA on hexane)

Sources & evidence

ORD record
ord-cbc2c3b3df704f6b81f3f3bcbaee0164
Source dataset
uspto-grants-2015_05
Patent number
US09029391B2

Reaction notes

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