Hydrazine → 1,3,4-Oxadiazol-2(3H)-one

HRID 1746144Notes

Reaction equation

HRID 1746144 reaction equation
[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[C:8]([OH:10])[CH:7]=[N:6][CH:5]=1.Br[C:13]1[CH:17]=[CH:16][O:15][N:14]=1.[NH2:18][NH2:19]>CO>[N:6]1[CH:5]=[CH:4][CH:9]=[C:8]([O:10][C:13]2[CH2:17][CH2:16][O:15][N:14]=2)[CH:7]=1.[O:2]1[CH:1]=[N:19][NH:18][C:3]1=[O:11]

Participants

6

Reactant 3

HCID 9321HydrazineHCID 354317Methyl 5-hydroxypyridine-3-carboxylateHCID 139338913-Bromo-1,2-oxazole

Product 2

HCID 184289921,3,4-Oxadiazol-2(3H)-oneHCID 668185323-(Pyridin-3-yloxy)-4,5-dihydroisoxazole

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-231a and I-231b were prepared in 3 steps according to the following procedures: 5-hydroxynicotinic acid methyl ester is reacted with racemic bromoisoxazole I-75 using Method 5. The resulting methyl ester (1.0 equiv) is dissolved in methanol (0.08 M) after which hydrazine (50 equiv, 50% by weight in water) is added and the reaction is allowed to stir for 14 h. The reaction mixture is then concentrated under vacuum and used directly in the next step. The hydrazide is dissolved in dioxane (0.12 M with respect to hydrazide). N,N-Carbonydiimidazole (1.2 equiv) is added and the reaction is sealed and heated to reflux for 4 h. The reaction is then transferred to a separatory funnel with excess ethyl acetate and water. The organic layer was washed water and brine, drive over sodium sulfate and concentrated under vacuum to provide crude material which was purified using flash silica gel chromatography (gradient methanol/dichloromethane) to provide the desired racemic 1,3,4-oxadiazol-2(3H)-one I-231. These compounds can be separated using chiral HPLC methods known in the art. For example, see chiral HPLC Method disclosed herein. [M+H]+=423.4 m/z. Activity: B

Workup

  1. additionis added
  2. concentrationThe reaction mixture is then concentrated under vacuum
  3. dissolutionThe hydrazide is dissolved in dioxane (0.12 M with respect to hydrazide)
  4. additionN,N-Carbonydiimidazole (1.2 equiv) is added
  5. customthe reaction is sealed
  6. temperatureheated
  7. temperatureto reflux for 4 h
  8. customThe reaction is then transferred to a separatory funnel with excess ethyl acetate and water
  9. washThe organic layer was washed water and brine, drive over sodium sulfate
  10. concentrationconcentrated under vacuum
  11. customto provide crude material which
  12. customwas purified

Sources & evidence

ORD record
ord-5fced16f46694c4f81b0c19b273c7f1d
Source dataset
uspto-grants-2015_10
Patent number
US09149465B2

Reaction notes

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