Potassium trimethylsilanolate → HCID 86702683, compound

HRID 1897861Notes

Reaction equation

HRID 1897861 reaction equation
C[Si](C)(C)[O-:3].[K+].[F:7][C:8]1[C:16](F)=[C:15]([CH3:18])[CH:14]=[C:13]([N+:19]([O-:21])=[O:20])[C:9]=1[C:10]([OH:12])=[O:11]>CC1OCCC1>[F:7][C:8]1[C:16]([OH:3])=[C:15]([CH3:18])[CH:14]=[C:13]([N+:19]([O-:21])=[O:20])[C:9]=1[C:10]([OH:12])=[O:11]

Participants

5

Reactant 3

HCID 23668039Potassium trimethylsilanolateHCID 86702684HCID 86702684, compound2×HCID 178504318HCID 178504318, compound

Product 1

HCID 86702683HCID 86702683, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent2×

Conditions

Temperature
22.5 °C

Procedure

To a 500 mL glass reactor equipped with mechanical stirrer, addition funnel, thermocouple, reflux condenser and nitrogen inlet is charged potassium trimethylsilanolate (TMSOK, 61.2 g, 0.48 mol, 3.2 eq) and 2-methyl tetrahydrofuran (240 mL) to form a suspension. The suspension is stirred at 20-25° C. 2,3-difluoro-4-methyl-6-nitrobenzoic acid (32.5 g, 0.15 mol, 1 eq) is dissolved in 2-MeTHF (75 mL). To the TMSOK suspension, the solution of 2,3-difluoro-4-methyl-6-nitrobenzoic acid is added. The addition is exothermic and the temperature of the reaction mixture rises to 40-50° C. during addition. After charging is complete, the jacket temperature is set at 65-70° C. The suspension is stirred for 2-3 hour, until HPLC sample shows complete conversion. The mixture is cooled down to room temp. The reaction is quenched with water (100 mL), and acidified to pH 1 with HCl aqueous solution (6M, 90 mL). The layers are separated. The upper organic layer is washed with water (150 mL), and distilled under vacuum to minimum volume. The dark brown residue is stirred in 200 mL of mixed solvent of toluene/methylcyclohexane (v/v, 2:1) to give a suspension. The slurry is filtered. The solid is dried under vacuum to provide the desired product, 2-fluoro-3-hydroxy-4-methyl-6-nitrobenzoic acid (29 g, 90% yield).

Workup

  1. customTo a 500 mL glass reactor equipped with mechanical stirrer, addition funnel
  2. temperaturethermocouple, reflux condenser and nitrogen inlet
  3. customto form a suspension
  4. additionThe addition
  5. additionthe temperature of the reaction mixture rises to 40-50° C. during addition
  6. customis set at 65-70° C
  7. stirringThe suspension is stirred for 2-3 hour, until HPLC sample
  8. temperatureThe mixture is cooled down to room temp
  9. customThe reaction is quenched with water (100 mL)
  10. customThe layers are separated
  11. washThe upper organic layer is washed with water (150 mL)
  12. distillationdistilled under vacuum to minimum volume
  13. stirringThe dark brown residue is stirred in 200 mL of mixed solvent of toluene/methylcyclohexane (v/v, 2:1)
  14. customto give a suspension
  15. filtrationThe slurry is filtered
  16. customThe solid is dried under vacuum

Sources & evidence

ORD record
ord-53d12be174b7497596a8fe14f79dced5
Source dataset
uspto-grants-2013_08
Patent number
US08519176B1

Reaction notes

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