Sodium Hydroxide → HCID 15408740, compound

HRID 2393785Notes

Reaction equation

HRID 2393785 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:27][CH3:28])=[C:6]([C:8]([F:26])([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=2[N+:23]([O-:25])=[O:24])[C:9]([O:11]C)=[O:10])[CH:7]=1.[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:27][CH3:28])=[C:6]([C:8]([F:26])([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:21])([F:22])[F:20])=[CH:15][C:14]=2[N+:23]([O-:25])=[O:24])[C:9]([OH:11])=[O:10])[CH:7]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 4917385Methyl (5-chloro-2-methoxyphenyl)(fluoro)[2-nitro-4-(trifluoromethyl)phenyl]acetate

Product 1

HCID 15408740HCID 15408740, compoundYield 96.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

In a 3-necked 5-L round-bottomed flask, equipped with a mechanical stirrer and thermocouple, was suspended 5-chloro-α-fluoro-2-methoxy-α-[2-nitro-4-(trifluoromethyl)phenyl]benzeneacetic acid, methyl ester (450 g, 1.067 mol) in methanol (2.0 L) and 1.0 N aqueous sodium hydroxide (1.10 L, 1.10 mol). The reaction mixture was stirred for 4.5 hours at about 50° C. to complete the hydrolysis (determined by HPLC analysis). The reaction mixture was cooled to room temperature and concentrated on a rotary evaporator to remove most of the methanol. The residue was partitioned between tert-butylmethylether/hexane (1.2 L/0.5L) and water (1.4 L) and extracted. The organic layer was back-extracted with water (500 mL). The combined aqueous layers were cooled in an ice bath and while stirring vigorously, acidified with concentrated hydrochloric acid to about pH 1 (about 110 mL). Preferably, seed crystals of the title compound were added resulting in crystallization/precipitation of the product. The material was filtered after stirring for 3 hours at 0° C., air and vacuum dried overnight to afford 418.1 g of the title compound (96% yield when corrected for solvent, 99.6% by HPLC). A sample was recrystallized from toluene/hexane (1:1.25 at about 5 mL/g) to afford pure title compound.

Workup

  1. customIn a 3-necked 5-L round-bottomed flask, equipped with a mechanical stirrer
  2. customthe hydrolysis (determined by HPLC analysis)
  3. temperatureThe reaction mixture was cooled to room temperature
  4. concentrationconcentrated on a rotary evaporator
  5. customto remove most of the methanol
  6. customThe residue was partitioned between tert-butylmethylether/hexane (1.2 L/0.5L) and water (1.4 L)
  7. extractionextracted
  8. extractionThe organic layer was back-extracted with water (500 mL)
  9. temperatureThe combined aqueous layers were cooled in an ice bath
  10. stirringwhile stirring vigorously
  11. additionPreferably, seed crystals of the title compound were added
  12. customresulting in crystallization/precipitation of the product
  13. filtrationThe material was filtered
  14. stirringafter stirring for 3 hours at 0° C.
  15. customair and vacuum dried overnight

Sources & evidence

ORD record
ord-4cb4a33c7db64a07b5dcb98f9cdb64d8
Source dataset
uspto-grants-1998_09
Patent number
US05808095

Reaction notes

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