Hydroxyamine hydrochloride → 5-{5-[2,6-Dimethyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenoxy]pentyl}-3-methylisoxazole

HRID 1681924Notes

Reaction equation

HRID 1681924 reaction equation
[CH3:1][C:2]1[CH:19]=[C:18]([C:20]#[N:21])[CH:17]=[C:16]([CH3:22])[C:3]=1[O:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]1[O:14][N:13]=[C:12]([CH3:15])[CH:11]=1.Cl.[NH2:24]O.O.O.O.[C:29]([O-:32])(=O)[CH3:30].[Na+]>C(O)C>[CH3:22][C:16]1[CH:17]=[C:18]([C:20]2[N:24]=[C:29]([CH3:30])[O:32][N:21]=2)[CH:19]=[C:2]([CH3:1])[C:3]=1[O:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]1[O:14][N:13]=[C:12]([CH3:15])[CH:11]=1

Participants

5

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 149818385-[5-(2,6-Dimethyl-4-cyanophenoxy)pentyl]-3-methylisoxazoleHCID 23665404Sodium Acetate Trihydrate

Product 1

HCID 150572975-{5-[2,6-Dimethyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenoxy]pentyl}-3-methylisoxazoleYield 32.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A suspension of 7.0 g 5-[5-(2,6-dimethyl-4-cyanophenoxy)pentyl]-3-methylisoxazole, 1.8 g hydroxylamine hydrochloride and 3.5 g sodium acetate trihydrate in 40 ml 95% ethanol was heated at reflux under nitrogen for two days. The reaction mixture was filtered, concentrated in vacuo, and the residue in 50 ml acetic anhydride was heated at reflux for 3 hrs. The reaction mixture was poured over ice/10% sodium hydroxide and extracted with ether. The ether extracts were washed with water and saturated sodium bicarbonate, dried (K2CO3), concentrated and subjected to flash filtration (silica gel 60, 3:1 hexane/ethyl acetate) followed by chromatography (MPLC, silica gel 60, 3:1 hexane/ethyl acetate). The resulting product was crystallized from isopropyl acetate/hexane to give 2.7 g 5-{5-[2,6-dimethyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenoxy]pentyl}-3-methylisoxazole, m.p. 45°-46° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux under nitrogen for two days
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated in vacuo
  5. temperaturethe residue in 50 ml acetic anhydride was heated
  6. temperatureat reflux for 3 hrs
  7. additionThe reaction mixture was poured over ice/10% sodium hydroxide
  8. extractionextracted with ether
  9. washThe ether extracts were washed with water and saturated sodium bicarbonate
  10. dry with materialdried (K2CO3)
  11. concentrationconcentrated
  12. filtrationsubjected to flash filtration (silica gel 60, 3:1 hexane/ethyl acetate)
  13. customThe resulting product was crystallized from isopropyl acetate/hexane

Sources & evidence

ORD record
ord-3d54a2b7da7448858256358f44a205d7
Source dataset
uspto-grants-1992_12
Patent number
US05175178

Reaction notes

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