Hydrochloric Acid → 5-(3,5-Dimethyl-benzylcarbamoyl)-thiophene-3-carboxylic acid ethyl ester

HRID 1837614Notes

Reaction equation

HRID 1837614 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]([C:11]([OH:13])=O)[S:9][CH:10]=1)=[O:5])[CH3:2].CN(C)CCCN=C=NCC.Cl.[CH3:26][C:27]1[CH:28]=[C:29]([CH:32]=[C:33]([CH3:35])[CH:34]=1)[CH2:30][NH2:31]>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]([C:11](=[O:13])[NH:31][CH2:30][C:29]2[CH:32]=[C:33]([CH3:35])[CH:34]=[C:27]([CH3:26])[CH:28]=2)[S:9][CH:10]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27362413,5-DimethylbenzylamineHCID 202775414-(Ethoxycarbonyl)thiophene-2-carboxylic acid

Product 1

HCID 695434975-(3,5-Dimethyl-benzylcarbamoyl)-thiophene-3-carboxylic acid ethyl esterYield 73.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

0.5 g 2-carboxy-thiophen-4-carboxylic acid ethyl ester (M. Janda, J. Srogl, M. Nemec, I. Stibor; Org. Prep. and Proced. Int. 3 (6) (1971) 295.) and 0.67 g N′-(3-dimethylaminopropyl)-N-ethylcarbodiimid×HCl are stirred in 50 mL DCM for 15 min. Then, 0.338 g 3,5-dimethylbenzylamin are added and the mixture is stirred overnight. The solution is extracted with 2N HCl and water, then evaporated. The residue is titurated with isohexan, and the resulting crystals are filtrated and air-dried, yielding 0.58 g (73%) crude 5-(3,5-Dimethyl-benzylcarbamoyl)-thiophene-3-carboxylic acid ethyl ester (7b). This ester in converted to title compound by reaction with hydroxylamine hydrochloride in a manner similar to that described for the conversion of 4b into 4a in example 4. After chromatography (silica, ethylacetate), thiophene-2,4-dicarboxylic acid 2-(3,5-dimethyl-benzylamide) 4-hydroxyamide (7a) is obtained as crystals; 44 mg, 9%, mp: 181° C. (decomp.).

Workup

  1. extractionThe solution is extracted with 2N HCl and water
  2. customevaporated
  3. filtrationthe resulting crystals are filtrated
  4. customair-dried

Sources & evidence

ORD record
ord-84921da024c8432f9171f14d453d8926
Source dataset
uspto-grants-2004_08
Patent number
US06784173B2

Reaction notes

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