Hydroxyamine hydrochloride → HCID 141568509, compound

HRID 2249199Notes

Reaction equation

HRID 2249199 reaction equation
[CH2:1]([N:3]([CH2:8][C:9]1[CH:14]=[C:13]([C:15](=O)[C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[CH:12]=[CH:11][C:10]=1[N+:24]([O-:26])=[O:25])[CH2:4][C:5]([OH:7])=[O:6])[CH3:2].Cl.[NH2:28][OH:29].[F-].[K+]>C(O)C>[CH2:1]([N:3]([CH2:8][C:9]1[CH:14]=[C:13](/[C:15](=[N:28]/[OH:29])/[C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[CH:12]=[CH:11][C:10]=1[N+:24]([O-:26])=[O:25])[CH2:4][C:5]([OH:7])=[O:6])[CH3:2]

Participants

5

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 522689Potassium FluorideHCID 67883749HCID 67883749, compound

Product 1

HCID 141568509HCID 141568509, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 26.7 parts of ethyl N-[[5-(4-methylbenzoyl)-2-nitrophenyl]methyl]glycine (which is a precursor to intermediate 50 in Example 9), 6.25 parts of hydroxylamine monohydrochloride, 5.25 parts of potassium fluoride and 395 parts of ethanol was stirred for 22 hours at reflux temperature. The reaction mixture was evaporated and the residue was dissolved in ethyl acetate. The whole was washed with sodium hydrogen carbonate solution 10% and with water. The organic layer was dried, filtered and evaporated and the residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH 98:2). The eluent of the E- and Z-isomer fractions was evaporated and the residue was crystallized from 2,2'-oxybispropane, yielding 3.7 parts of product. The mother liquor was evaporated and the residue was isomerized in a mixture of 1,4-dioxane and 2-propanol, saturated with HCl, by stirring overnight. The solvent was evaporated and the residue was stirred in water. After neutralizing with NaHCO3 10%, the product was extracted with dichloromethane. The extract was dried, filtered and evaporated and the residue was crystallized from 2,2'-oxybispropane, yielding 2 additional fractions of resp. 3.6 parts and 1.2 parts of product. The three fractions were recrystallized from a mixture of ethyl acetate and 2,2'-oxybispropane, yielding 5.3 parts (19%) of ethyl (E)-N-[[5-[(hydroxyimino) (4-methylphenyl)methyl]-2-nitrophenyl]methyl]glycine (interm. 57).

Workup

  1. temperatureat reflux temperature
  2. customThe reaction mixture was evaporated
  3. dissolutionthe residue was dissolved in ethyl acetate
  4. washThe whole was washed with sodium hydrogen carbonate solution 10% and with water
  5. customThe organic layer was dried
  6. filtrationfiltered
  7. customevaporated
  8. customthe residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH 98:2)
  9. customThe eluent of the E- and Z-isomer fractions was evaporated
  10. customthe residue was crystallized from 2,2'-oxybispropane
  11. customyielding 3.7 parts of product
  12. customThe mother liquor was evaporated
  13. additionthe residue was isomerized in a mixture of 1,4-dioxane and 2-propanol, saturated with HCl
  14. stirringby stirring overnight
  15. customThe solvent was evaporated
  16. stirringthe residue was stirred in water
  17. extractionthe product was extracted with dichloromethane
  18. customThe extract was dried
  19. filtrationfiltered
  20. customevaporated
  21. customthe residue was crystallized from 2,2'-oxybispropane
  22. customyielding 2 additional fractions of resp
  23. customThe three fractions were recrystallized from a mixture of ethyl acetate and 2,2'-oxybispropane

Sources & evidence

ORD record
ord-037821fdbb604116a1f717edc661033d
Source dataset
uspto-grants-1991_08
Patent number
US05043327

Reaction notes

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