Ethyl Thioglycolate → 3-Hydroxy-thieno[2,3-c]pyridine-2-carboxylic acid ethyl ester

HRID 1366780Notes

Reaction equation

HRID 1366780 reaction equation
C(O[C:4](=[O:12])[C:5]1[CH:10]=[CH:9][N:8]=[CH:7][C:6]=1Cl)C.[CH2:13]([O:15][C:16](=[O:19])[CH2:17][SH:18])[CH3:14].[H-].[Na+]>CN(C=O)C>[CH2:13]([O:15][C:16]([C:17]1[S:18][C:6]2=[CH:7][N:8]=[CH:9][CH:10]=[C:5]2[C:4]=1[OH:12])=[O:19])[CH3:14]

Participants

5

Reactant 3

HCID 12185Ethyl ThioglycolateHCID 24758Sodium hydrideHCID 2762498Ethyl 3-chloroisonicotinate

Product 1

HCID 597038773-Hydroxy-thieno[2,3-c]pyridine-2-carboxylic acid ethyl esterYield 99.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
5 °C

Procedure

To a cooled (5° C.) stirred solution of 3-chloro-isonicotinic acid ethyl ester (1.11 g, 6.0 mmol) and mercapto-acetic acid ethyl ester (1.8 ml, 16.7 mmol) in anhydrous DMF (20 ml), under an argon atmosphere, was added sodium hydride (15.6 mmol, 60% dispersion in oil, 622 mg) in portions over 20 minutes. Stirring was continued at 5° C. for 20 minutes, followed by 18 hours at room temperature. The reaction mixture was then quenched by the addition of water (5 ml), acidified by the addition of acetic acid (1 ml), and subsequently concentrated to provide a residue. The residue was partitioned between ethyl acetate (150 ml) and water (50 ml). The organic phase was isolated, dried over sodium sulphate, filtered and evaporated to give a yellow oil. The oil was purified by flash chromatography (Si-SPE, pentane:ethyl acetate, gradient 80:20 to 30:70) to afford the title compound as a yellow solid (1.33 g, 99%). LCMS (method B): RT=2.57 min, M+H+=224.

Workup

  1. waitfollowed by 18 hours at room temperature
  2. customThe reaction mixture was then quenched by the addition of water (5 ml)
  3. additionacidified by the addition of acetic acid (1 ml)
  4. concentrationsubsequently concentrated
  5. customto provide a residue
  6. customThe residue was partitioned between ethyl acetate (150 ml) and water (50 ml)
  7. customThe organic phase was isolated
  8. dry with materialdried over sodium sulphate
  9. filtrationfiltered
  10. customevaporated
  11. customto give a yellow oil
  12. customThe oil was purified by flash chromatography (Si-SPE, pentane:ethyl acetate, gradient 80:20 to 30:70)

Sources & evidence

ORD record
ord-df21000192154765b9f4594b643bdd36
Source dataset
uspto-grants-2011_02
Patent number
US07893085B2

Reaction notes

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