Sodium Hydroxide → HCID 178425475, compound

HRID 968835Notes

Reaction equation

HRID 968835 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:13](=[O:14])[N:12](C)[C:11]([CH2:16][CH2:17][CH2:18][C:19]3[CH:33]=[CH:32][C:22]([O:23][C:24]([CH3:31])([CH3:30])[C:25]([O:27]CC)=[O:26])=[CH:21][CH:20]=3)=[N:10]2)=[CH:4][CH:3]=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[C:13](=[O:14])[N:12]=[C:11]([CH2:16][CH2:17][CH2:18][C:19]3[CH:20]=[CH:21][C:22]([O:23][C:24]([CH3:31])([CH3:30])[C:25]([OH:27])=[O:26])=[CH:32][CH:33]=3)[NH:10]2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 68915869HCID 68915869, compound

Product 1

HCID 178425475HCID 178425475, compoundYield 95.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A 4-neck flask was equipped with overhead stirring apparatus and thermometer probe. The flask was charged with 2-(4-{3-[1-(4-Methylphenylmethyl)-4-methyl-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-yl]-propyl}phenoxy)-2-methyl-propionic acid, ethyl ester (800 g, 1.828 moles), and toluene (4000 mL) followed by 1N NaOH (4023 mL, 2.194 mol, 1.2 eq). The resulting mixture was stirred at ambient temperature for 5 h. The mixture was transferred to a 22-L bottom outlet flask and layers separated. The aqueous layer from the above layer separation was charged to the flask and acidified to pH 2 with concentrated HCl (337 mL). Ethyl acetate was added (8000 mL) and the mixture was transferred to a 22-L bottom-outlet flask. The layers were separated and the organic solution was transferred to a 22- L 3-neck round-bottom flask equipped with a distillation head and overhead stirring apparatus. The mixture was concentrated by distillation of the ethyl acetate to approximately 4000 mL, and fresh ethyl acetate (3600 mL) was added to the reaction vessel. Distillation was continued until 3600 mL of distillate were recovered. Heating was stopped and the mixture was allowed to cool slowly to 60-65° C., at which point seed crystals (0.8 g) of the desired product were added. The flask contents were allowed to cool slowly until crystallization initiated (55-57° C.), then the mixture was cooled to 0-5° C. and stirred for 1 h. The product was filtered, washed with cold ethyl acetate, and dried in vacuo at 55° C. to afford the title compound as a white solid (713.6 g, 95.3%). 1H NMR (DMSO-d6, 500 MHz): δ 1.46 (s, 6 H), 1.79 (m, 2 H), 2.25 (s, 3H), 2.35 (t, 2 H), 2.47 (t, 2 H), 4.70 (s, 2 H), 6.71 (d, 2H), 7.03 (d, 2H), 7.10 (m, 4 H). 13C NMR (DMSO-d6), δ 20.6, 25.0, 25.5, 27.7, 47.0, 78.3, 118.6, 127.4, 127.7, 128.9, 128.9, 134.4, 134.5, 136.4, 145.9, 153.4, 154.3, 175.0.

Workup

  1. customA 4-neck flask was equipped with overhead stirring apparatus and thermometer probe
  2. customThe mixture was transferred to a 22-L bottom outlet flask
  3. customlayers separated
  4. customThe aqueous layer from the above layer separation
  5. additionwas charged to the flask
  6. additionEthyl acetate was added (8000 mL)
  7. customthe mixture was transferred to a 22-L bottom-outlet flask
  8. customThe layers were separated
  9. customequipped with a distillation head and overhead
  10. stirringstirring apparatus
  11. concentrationThe mixture was concentrated by distillation of the ethyl acetate to approximately 4000 mL, and fresh ethyl acetate (3600 mL)
  12. additionwas added to the reaction vessel
  13. distillationDistillation
  14. customwere recovered
  15. temperatureHeating
  16. temperatureto cool slowly to 60-65° C., at which point seed crystals (0.8 g) of the desired product
  17. additionwere added
  18. temperatureto cool slowly until crystallization
  19. custom(55-57° C.)
  20. temperaturethe mixture was cooled to 0-5° C.
  21. stirringstirred for 1 h
  22. filtrationThe product was filtered
  23. washwashed with cold ethyl acetate
  24. customdried in vacuo at 55° C.

Sources & evidence

ORD record
ord-259900e22fd84fd18dca07e64c052333
Source dataset
uspto-grants-2007_12
Patent number
US07304062B2

Reaction notes

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