Ethyl Thioglycolate → HCID 21083973, compound

HRID 347903Notes

Reaction equation

HRID 347903 reaction equation
SCC(OCC)=O.[H-].[Na+].[H][H].[C:12]([C:20]1[C:21]([S:26][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])=[N:22][CH:23]=[CH:24][CH:25]=1)(=O)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>CN(C=O)C>[C:13]1([C:12]2[C:20]3[C:21](=[N:22][CH:23]=[CH:24][CH:25]=3)[S:26][C:27]=2[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 12185Ethyl ThioglycolateHCID 24758Sodium hydrideHCID 21083969HCID 21083969, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 21083973HCID 21083973, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of ethyl 2-mercaptoacetate (0.6 mL, 5.5 mmol) in dry DMF (10 mL) under nitrogen and cooled with an ice bath was added sodium hydride (220 mg of 60% dispersion in oil, 5.75 mmol). After hydrogen evolution had ceased the cooling bath was removed and the reaction stirred at room temperature for 30 mins. A solution of Intermediate 1 (920 mg, 4.6 mmol) in DMF (5 mL) was added and the reaction stirred at room temperature for 3 h. The reaction was quenched with water (50 mL) and extracted with EtOAc (3×50 mL). The combined EtOAc layers were washed with brine (50 mL), dried (MgSO4) and concentrated in vacuo to give a mixture of the title compound and uncyclised ethyl 2-(3-benzoylpyridin-2-ylsulfanyl)acetate. This crude mixture was dissolved in EtOH (10 mL) and sodium ethoxide (10 mL of 0.5M solution in EtOH, 5.0 mmol) added. The reaction was stirred at room temperature for 45 mins after which time complete conversion of uncyclised material to title compound was observed. The reaction was diluted with EtOAc (50 mL), washed with water (20 mL), dried (MgSO4) and concentrated in vacuo. The crude product was purified by chromatography on silica (10% EtOAc in isohexane) to give the title compound as a white solid (780 mg, 60%). δH (CDCl3) 8.63 (1H, dd, J 4.5, 1.4 Hz), 7.78 (1H, dd, J 8.2, 1.5 Hz), 7.41 (3H, m), 7.33–7.32 (2H, m), 7.24 (1H, dd, J 8.2, 4.6 Hz), 4.18 (2H, q, J 7.1 Hz), 1.15 (3H, t, J 7.1 Hz) LCMS (ES+) RT 3.90 minutes, 284 (M+H)+.

Workup

  1. customwas removed
  2. stirringthe reaction stirred at room temperature for 3 h
  3. customThe reaction was quenched with water (50 mL)
  4. extractionextracted with EtOAc (3×50 mL)
  5. washThe combined EtOAc layers were washed with brine (50 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customto give

Sources & evidence

ORD record
ord-c9252df97e654f21a985e46f7d765a7e
Source dataset
uspto-grants-2007_02
Patent number
US07176215B2

Reaction notes

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