Dimethylformamide → Methyl 7-(trifluoromethyl)-1-benzothiophene-2-carboxylate

HRID 1504577Notes

Reaction equation

HRID 1504577 reaction equation
F[C:2]1[C:9]([C:10]([F:13])([F:12])[F:11])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.[C:14]([O:18][CH3:19])(=[O:17])[CH2:15][SH:16].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[F:11][C:10]([F:13])([F:12])[C:9]1[C:2]2[S:16][C:15]([C:14]([O:18][CH3:19])=[O:17])=[CH:4][C:3]=2[CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 16907Methyl ThioglycolateHCID 5179782-Fluoro-3-(trifluoromethyl)benzaldehyde

Product 1

HCID 18526203Methyl 7-(trifluoromethyl)-1-benzothiophene-2-carboxylateYield 41.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 600 mg of 2-fluoro-3-(trifluoromethyl)benzaldehyde, 398 mg of methyl thioglycolate, 694 mg of potassium carbonate and 10 ml of DMF was stirred at 140° C. for 2 hours. The reaction mixture was cooled down to room temperature. To the reaction mixture was added water, and the mixture was washed with tert-butyl methyl ether three times. To the aqueous layer was added hydrochloric acid, then, the mixture was extracted with tert-butyl methyl ether three times. The combined organic layers were washed with water and saturated saline, and dried over magnesium sulfate, then, concentrated under reduced pressure. To the residue was added water to cause deposition of a solid which was then collected by filtration, and dried under reduced pressure. To the resultant solid were added 20 ml of methanol and 0.31 ml of oxalyl chloride, and the mixture was stirred at 80° C. for 2 hours. The reaction mixture was cooled down to room temperature, then, concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, to obtain 338 mg of methyl 7-(trifluoromethyl)benzo[b]thiophene-2-carboxylate (present condensed ring compound 4).

Workup

  1. temperatureThe reaction mixture was cooled down to room temperature
  2. washthe mixture was washed with tert-butyl methyl ether three times
  3. additionTo the aqueous layer was added hydrochloric acid
  4. extractionthe mixture was extracted with tert-butyl methyl ether three times
  5. washThe combined organic layers were washed with water and saturated saline
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. additionTo the residue was added water
  9. filtrationwas then collected by filtration
  10. customdried under reduced pressure
  11. additionTo the resultant solid were added 20 ml of methanol and 0.31 ml of oxalyl chloride
  12. stirringthe mixture was stirred at 80° C. for 2 hours
  13. temperatureThe reaction mixture was cooled down to room temperature
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f2af1244c0c04c9d867ca9618294e522
Source dataset
uspto-grants-2015_12
Patent number
US09215871B2

Reaction notes

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