Hydrochloric Acid → HCID 20226387, compound

HRID 1731999Notes

Reaction equation

HRID 1731999 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]=[CH:13][C:14]=1[NH2:15])[C:5]([CH:7]([CH3:11])[C:8]([OH:10])=O)=O.[CH2:16]=[O:17].[OH-].[Na+].Cl.O.[NH2:22][NH2:23]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[CH:7]([CH2:8][OH:10])[CH2:11][C:16](=[O:17])[NH:22][N:23]=2)[CH:12]=[CH:13][C:14]=1[NH2:15]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 70424667HCID 70424667, compound

Product 1

HCID 20226387HCID 20226387, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

45 g of 3-chloro-4-amino-benzoyl-propionic acid are stirred together with 50 ml of 35% formaldehyde solution and 440 ml of 0.5N sodium hydroxide solution for 17 hours at room temperature. The reaction mixture is adjusted with 2N hydrochloric acid to pH 5, and is extracted with ethyl acetate. The ethyl acetate phases are washed with water, dried over sodium sulfate and concentrated by evaporation. The residue, 3-(3-chloroamino-benzoyl)-3-hydroxymethyl)-propionic acid, is directly further reacted unpurified by being refluxed together with 1600 ml of ethanol and 18 ml of hydrazine hydrate for 5 hours. The reaction mixture is concentrated by evaporation, and the residue is distributed between 4N hydrochloric acid and ethyl acetate. The aqueous phases are rendered basic with a 2N sodium carbonate solution, and are extracted with ethyl acetate. The ethyl acetate extracts are washed twice with 2N sodium carbonate solution and with water, dried and then concentrated by evaporation. As residue is obtained the crude 6-(3-chloro-4-amino-phenyl)- 5-hydroxymethyl-4,5-dihydro-3(2H)-pyridazinone, which together with 25 g of β,β-dibromodiethyl ether and 37 ml of diisopropylethylamine in 150 ml of dimethylformamide are refluxed for 18 hours. The reaction mixture is concentrated under high vacuum in a rotary evaporator; the residue is then taken up in ethyl acetate, and repeatedly washed with 1N hydrochloric acid and water. The organic phase is dried over sodium sulfate and concentrated by evaporation, the product which crystallises out being 6-(3-chloro-4-morpholino-phenyl)-5-hydroxymethyl-4,5-dihydro-3(2H)-pyridazinone, m.p. 172°-173° C.

Workup

  1. extractionis extracted with ethyl acetate
  2. washThe ethyl acetate phases are washed with water
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated by evaporation
  5. customThe residue, 3-(3-chloroamino-benzoyl)-3-hydroxymethyl)-propionic acid, is directly further reacted unpurified
  6. concentrationThe reaction mixture is concentrated by evaporation
  7. extractionare extracted with ethyl acetate
  8. washThe ethyl acetate extracts are washed twice with 2N sodium carbonate solution and with water
  9. customdried
  10. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-f268c3a021fb4e018a9a5406f88320c5
Source dataset
uspto-grants-1986_11
Patent number
US04624951

Reaction notes

Loading…