Hydrochloric Acid → HCID 54689879, compound

HRID 1244099Notes

Reaction equation

HRID 1244099 reaction equation
C(OC([C:6]1[C:10]([C:11]2[CH:16]=[C:15]([Cl:17])[C:14]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[C:13]([Cl:26])[CH:12]=2)=[CH:9][S:8][C:7]=1[NH:27][C:28](=[O:34])[CH2:29][C:30](OC)=[O:31])=O)C.[H-].[Na+].Cl.C(OCC)C>C1COCC1>[Cl:26][C:13]1[CH:12]=[C:11]([C:10]2[C:6]3[C:30]([OH:31])=[CH:29][C:28](=[O:34])[NH:27][C:7]=3[S:8][CH:9]=2)[CH:16]=[C:15]([Cl:17])[C:14]=1[O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl Ether2×HCID 24758Sodium hydrideHCID 69607337HCID 69607337, compound

Product 1

HCID 54689879HCID 54689879, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1.91 g (3.65 mmol) of 4-(4-benzyloxy-3,5-dichloro-phenyl)-2-(2-methoxycarbonyl-acetylamino)-thiophene-3-carboxylic acid ethyl ester in 20 mL of THF was added 600 mg (15 mmol) of 60% NaH in mineral oil. The reaction was stirred at reflux under N2 for 18 h, then the excess NaH was quenched by the addition of 10 mL of water. The THF was removed in vacuo, then the remaining solution was taken up in 30 mL of 2M NaOH(aq.) and 30 mL of ethanol. This was stirred at 80° C. for 5 h, then concentrated to remove most of the ethanol. The remaining solution was diluted with 100 mL of water, and extracted with diethyl ether (2×30 mL). The ether layers were discarded, along with a small amount of precipitate that formed in the aqueous layer. The stirred aqueous layer was made acidic with 4M HCl to give a precipitate. Diethyl ether was added and the mixture was stirred to suspend the precipitate in the ether layer, then most of the water was decanted. The precipitate was filtered, and washed with water, then diethyl ether to give 1.20 g (79%) of the titled compound as a tan solid. MS (ESI) m/e 417.7, (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 5.05 (s, 1H) 5.76 (s, 1H) 7.23 (s, 1H) 7.43 (m, 2H) 7.58 (m, 2H) 11.15 (s, 1H).

Workup

  1. temperatureat reflux under N2 for 18 h
  2. customthe excess NaH was quenched by the addition of 10 mL of water
  3. customThe THF was removed in vacuo
  4. stirringThis was stirred at 80° C. for 5 h
  5. concentrationconcentrated
  6. customto remove most of the ethanol
  7. additionThe remaining solution was diluted with 100 mL of water
  8. extractionextracted with diethyl ether (2×30 mL)
  9. customthat formed in the aqueous layer
  10. customto give a precipitate
  11. stirringthe mixture was stirred
  12. custommost of the water was decanted
  13. filtrationThe precipitate was filtered
  14. washwashed with water

Sources & evidence

ORD record
ord-1d3029e9ff854fcf91b8a0e65ab70951
Source dataset
uspto-grants-2006_10
Patent number
US07119205B2

Reaction notes

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