5-methyl-1H-pyrazole-3-carboxylic acid → HCID 53972348, compound

HRID 1763936Notes

Reaction equation

HRID 1763936 reaction equation
ClC(OCC)=O.[CH3:7][C:8]1[NH:12][N:11]=[C:10]([C:13]([OH:15])=O)[CH:9]=1.Cl.[NH2:17][CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][C:28]([O:30]CC)=[O:29])=[CH:22][CH:21]=1.[OH-].[Na+]>C(O)C.C(N(CC)CC)C.O1CCCC1>[CH3:7][C:8]1[NH:12][N:11]=[C:10]([C:13]([NH:17][CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][C:28]([OH:30])=[O:29])=[CH:22][CH:21]=2)=[O:15])[CH:9]=1

Participants

8

Reactant 4

HCID 98225-methyl-1H-pyrazole-3-carboxylic acidHCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 20463439Ethyl 3-[4-(2-aminoethyl)phenyl]propanoate--hydrogen chloride (1/1)

Product 1

HCID 53972348HCID 53972348, compoundYield 22%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent2×

Procedure

1.27 ml. triethylamine and 0.85 ml. ethyl chloroformate are added at -10° C. to a solution of 1.12 g. of 5-methylpyrazole-3-carboxylic acid in 25 ml. anhydrous tetrahydrofuran. After 15 minutes, a further 1.27 ml. triethylamine is added and then 2.57 g. ethyl β-[4-(2-aminoethyl)-phenyl]-propionate hydrochloride. The reaction mixture is stirred for 1 hour at +20° C., filtered with suction and the filtrate is evaporated and the residue taken up in methylene chloride. After extraction with 2N hydrochloric acid, 2N aqueous sodium hydroxide solution and neutralization, the solution is dried and evaporated. The crude ester thus obtained is heated under reflux for 1 hour with 0.6 g. sodium hydroxide in 30 ml. ethanol. After cooling, the precipitated sodium salt is filtered off with suction, dissolved in water and carefully acidified. The precipitate obtained is filtered off and recrystallized from 20% ethanol. There is obtained β-{4-[2-(5-methylpyrazole- 3-carboxamido)-ethyl]-phenyl}-propionic acid in a yield of 22% of theory; m.p. 202°-205° C.

Workup

  1. filtrationfiltered with suction
  2. customthe filtrate is evaporated
  3. extractionAfter extraction with 2N hydrochloric acid, 2N aqueous sodium hydroxide solution and neutralization
  4. customthe solution is dried
  5. customevaporated
  6. customThe crude ester thus obtained
  7. temperatureis heated
  8. temperatureunder reflux for 1 hour with 0.6 g
  9. temperatureAfter cooling
  10. filtrationthe precipitated sodium salt is filtered off with suction
  11. dissolutiondissolved in water
  12. customThe precipitate obtained
  13. filtrationis filtered off
  14. customrecrystallized from 20% ethanol

Sources & evidence

ORD record
ord-116d710299ad415ea1bfed0e46dd2a20
Source dataset
uspto-grants-1978_09
Patent number
US04113871

Reaction notes

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