Ethyl Propionate → HCID 178430505, compound

HRID 2291340Notes

Reaction equation

HRID 2291340 reaction equation
[F:1][C:2]([F:23])([F:22])[CH2:3][N:4]=[C:5]([NH2:21])[NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:14][CH2:15][CH2:16][C:17](=[NH:20])OC)[N:8]=1.[Cl-].[NH4+:25].[Na].[CH:27]([CH:29]([CH3:35])[C:30]([O:32]CC)=[O:31])=[O:28].C([O:38][CH:39]=[O:40])C.C(OCC)(=O)CC.[H-].[Na+]>CO>[C:39]([OH:40])(=[O:38])/[CH:35]=[CH:29]\[C:30]([OH:32])=[O:31].[OH:28][C:27]1[C:29]([CH3:35])=[CH:30][N:20]=[C:17]([CH2:16][CH2:15][CH2:14][O:13][C:9]2[N:8]=[C:7]([NH:6][C:5]([NH2:21])=[N:4][CH2:3][C:2]([F:1])([F:22])[F:23])[CH:12]=[CH:11][CH:10]=2)[N:25]=1

Participants

9

Reactant 7

HCID 7749Ethyl PropionateHCID 8025Ethyl formateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 5360545SodiumHCID 10898741Ethyl 2-FormylpropionateHCID 21279797HCID 21279797, compound

Product 1

HCID 178430505HCID 178430505, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of methyl 4-[2-(2-[2,2,2-trifluoroethyl]guanidino)pyrid-6-yloxy]butyrimidate (0.3 g.), ammonium chloride (0.054 g.) and MeOH (5 ml.) was stirred at room temperature for 1 hour. The mixture was treated with the sodium salt of ethyl 2-formylpropionate [prepared from ethylformate (0.37 g.), ethyl propionate (0.51 g.) and a 50% w/w dispersion of sodium hydride in oil (0.5 g.) as in the first part of Example 11] and heated under reflux for 18 hours and then evaporated to dryness. The residue was partitioned between ether and H2O and the aqueous phase acidified to pH 1 and washed with ether. The aqueous phase was neutralised with NaHCO3 and extracted three times with EtOAc, and the combined EtOAc extracts dried and evaporated to dryness. A solution of the residue in acetone was added to a solution of maleic acid in acetone and the precipitate collected and crystallised from aqueous EtOH to give 4-hydroxy-5-methyl-2-(3-[2-(2-[2,2,2-trifluoroethyl]guanidino)pyrid-6-yloxy]propyl)pyrimidine hydrogen maleate (0.1 g.), m.p. 209°-210°.

Workup

  1. temperatureunder reflux for 18 hours
  2. customevaporated to dryness
  3. customThe residue was partitioned between ether and H2O
  4. washwashed with ether
  5. extractionextracted three times with EtOAc
  6. dry with materialthe combined EtOAc extracts dried
  7. customevaporated to dryness
  8. additionA solution of the residue in acetone was added to a solution of maleic acid in acetone
  9. customthe precipitate collected
  10. customcrystallised from aqueous EtOH

Sources & evidence

ORD record
ord-0ecf3f938158438ab373c7ae87614b0a
Source dataset
uspto-grants-1989_01
Patent number
US04795755

Reaction notes

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