Phosphorus oxychloride → 3-Methyl-thieno[3,2-b]pyridine-6-carboxylic acid ethyl ester

HRID 1773538Notes

Reaction equation

HRID 1773538 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7](=O)[C:8]2[S:14][CH:13]=[C:12]([CH3:15])[C:9]=2[NH:10][CH:11]=1)=[O:5])[CH3:2].P(Cl)(Cl)(Cl)=O>C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[S:14][CH:13]=[C:12]([CH3:15])[C:9]2=[N:10][CH:11]=1)=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 225743463-methyl-6-ethoxycarbonylthieno[3,2-b]pyridin-7(4H)-one

Product 1

HCID 580561733-Methyl-thieno[3,2-b]pyridine-6-carboxylic acid ethyl esterYield 83.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 3-methyl-7-oxo-4,7-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid ethyl ester (WO 2003/059878 A2) (1.0 g) and phosphorus oxychloride (3 mL) was heated at 150° C. for 15 minutes in a microwave reactor. The reaction mixture was then cooled and poured into a mixture of ice-water and ethyl acetate. The resulting mixture was stirred for 10 minutes; the organic layer was separated, washed twice with water (50 mL) and with brine, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. To the solid residue dissolved in a mixture of ethyl acetate and isopropanol (10/1, 55 mL) sodium acetate trihydrate (2.0 g) and palladium hydroxide on carbon (20%, 0.3 g) were added and the resulting mixture was shaken in a Parr apparatus under hydrogen atmosphere (50 PSI) overnight. The reaction mixture was then filtered on a CELITE™ pad, the filtrate was evaporated under reduced pressure and the crude residue was purified by flash chromatography (EtOAc/hexane, 10/90) to afford 0.78 g of 3-methyl-thieno[3,2-b]pyridine-6-carboxylic acid ethyl ester.

Workup

  1. temperatureThe reaction mixture was then cooled
  2. customthe organic layer was separated
  3. washwashed twice with water (50 mL) and with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. dissolutionTo the solid residue dissolved in a mixture of ethyl acetate and isopropanol (10/1, 55 mL) sodium acetate trihydrate (2.0 g) and palladium hydroxide on carbon (20%, 0.3 g)
  8. additionwere added
  9. stirringthe resulting mixture was shaken in a Parr apparatus under hydrogen atmosphere (50 PSI) overnight
  10. filtrationThe reaction mixture was then filtered on a CELITE™ pad
  11. customthe filtrate was evaporated under reduced pressure
  12. customthe crude residue was purified by flash chromatography (EtOAc/hexane, 10/90)

Sources & evidence

ORD record
ord-9ef1aa21ee114950b673689e8c22f943
Source dataset
uspto-grants-2016_02
Patent number
US09255110B2

Reaction notes

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