Methane → 6-Methyl-1-benzothiophene-2-carboxylic acid

HRID 1971864Notes

Reaction equation

HRID 1971864 reaction equation
C.C([O-])=O.[NH4+].Cl[C:7]1[C:8]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][C:9]=2[S:10][C:11]=1[C:12]([OH:14])=[O:13].[OH-].[Na+]>CO.O.[Pd]>[CH3:19][C:16]1[CH:17]=[CH:18][C:8]2[CH:7]=[C:11]([C:12]([OH:14])=[O:13])[S:10][C:9]=2[CH:15]=1

Participants

8

Reactant 4

HCID 297MethaneHCID 14798Sodium HydroxideHCID 8151853-Chloro-6-methyl-1-benzothiophene-2-carboxylic acidHCID 2723923Ammonium formate2×

Product 1

HCID 128138506-Methyl-1-benzothiophene-2-carboxylic acidYield 95%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalyst2×HCID 887MethanolSolvent3×HCID 962WaterSolvent

Procedure

A suspension of palladium on 5% wet charcoal (50% water) (1.065 g) and ammonium formate (2.52 g) in methanol (30 ml) is stirred for 20 minutes in an inert atmosphere; a solution of 2.52 g of ammonium formate in 5 ml of water and a solution consisting of 2.26 g of 3-chloro-6-methyl-benzo[b]thiophene-2-carboxylic acid (18), 70 ml of methanol and 10 ml of 1N NaOH is then added. The mixture is kept under reflux stirring in an inert atmosphere for 15 hours. 0.425 g of Pd/C (5% wet) is then added, and the reaction mixture is again maintained under reflux for 24 hours. The mixture is then cooled, diluted with methanol, filtered through a Celite bed, and the catalyst is washed with further methanol. The filtrate is then evaporated until dry at low pressure and the residue treated with 70 ml of 1N HCl and 250 ml of ethyl acetate. The organic phase is washed with brine (3×) and evaporated until dry, to obtain 1.82 g of compound (1) in the form of a white solid; HPLC purity=98.2%, yield=94.7%.

Workup

  1. additionis then added
  2. temperatureunder reflux
  3. stirringstirring in an inert atmosphere for 15 hours
  4. temperaturethe reaction mixture is again maintained
  5. temperatureunder reflux for 24 hours
  6. temperatureThe mixture is then cooled
  7. filtrationfiltered through a Celite bed
  8. washthe catalyst is washed with further methanol
  9. customThe filtrate is then evaporated
  10. customuntil dry at low pressure
  11. additionthe residue treated with 70 ml of 1N HCl and 250 ml of ethyl acetate
  12. washThe organic phase is washed with brine (3×)
  13. customevaporated
  14. customuntil dry

Sources & evidence

ORD record
ord-ffc24dbf162543568d131bb53edb9c74
Source dataset
uspto-grants-2013_04
Patent number
US08431684B2

Reaction notes

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