Sodium hydride → HCID 54689835, compound

HRID 1244101Notes

Reaction equation

HRID 1244101 reaction equation
C(OC([C:6]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:13][CH:12]=2)=[CH:9][S:8][C:7]=1[NH:25][C:26](=[O:33])[CH2:27][C:28](OCC)=[O:29])=O)C.[H-].[Na+]>C1COCC1>[CH2:18]([O:17][C:14]1[CH:15]=[CH:16][C:11]([C:10]2[C:6]3[C:28]([OH:29])=[CH:27][C:26](=[O:33])[NH:25][C:7]=3[S:8][CH:9]=2)=[CH:12][CH:13]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 69607382HCID 69607382, compound

Product 1

HCID 54689835HCID 54689835, compoundYield 77.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4.42 g (9.45 mmol) of 4-(4-benzyloxy-phenyl)-2-(2-ethoxycarbonyl-acetylamino)-thiophene-3-carboxylic acid ethyl ester from Example 7c in 50 mL of THF was added 1.6 g (40 mmol) of 60% NaH in mineral oil. The mixture was stirred at reflux under N2 for 17 h, then the excess NaH was quenched by the addition of 25 mL H2O. The reaction was concentrated in vacuo to remove most of the THF, then the remaining mixture was taken up in 75 mL of 2M NaOH and 75 mL of ethanol and heated at reflux for 6.5 h. The ethanol was removed in vacuo, and the aqueous solution was diluted with water to a total volume of 150 mL. The solution was extracted with diethyl ether (3×30 mL) to remove the mineral oil, then the aqueous layer was filtered through diatomaceous earth to remove some cloudiness. The solution was made acidic by addition of 80 mL of 4M HCl, and filtered after bubbling had ceased (about 5 min). The precipitate was washed with water, then dried on the filter to give 2.55 g (77%) of a tan solid as the titled compound. MS (ESI) m/e 350, (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 5.13 (s, 2H) 5.70 (s, 1H) 6.92 (s, 1H) 6.98 (m, 2H) 7.40 (m, 7H) 10.82 (s, 1H).

Workup

  1. temperatureat reflux under N2 for 17 h
  2. customthe excess NaH was quenched by the addition of 25 mL H2O
  3. concentrationThe reaction was concentrated in vacuo
  4. customto remove most of the THF
  5. temperature75 mL of ethanol and heated
  6. temperatureat reflux for 6.5 h
  7. customThe ethanol was removed in vacuo
  8. additionthe aqueous solution was diluted with water to a total volume of 150 mL
  9. extractionThe solution was extracted with diethyl ether (3×30 mL)
  10. customto remove the mineral oil
  11. filtrationthe aqueous layer was filtered through diatomaceous earth
  12. customto remove some cloudiness
  13. additionThe solution was made acidic by addition of 80 mL of 4M HCl
  14. filtrationfiltered
  15. customafter bubbling
  16. custom(about 5 min)
  17. washThe precipitate was washed with water
  18. customdried on the
  19. filtrationfilter

Sources & evidence

ORD record
ord-c94fd6072a3a4e5eb1a93d17c2cb5dde
Source dataset
uspto-grants-2006_10
Patent number
US07119205B2

Reaction notes

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