Hydrazine → Oxadiazole

HRID 1746141

Reaction equation

HRID 1746141 reaction equation
COC(=O)[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([OH:10])[CH:5]=1.Br[C:13]1[CH:17]=[CH:16][O:15][N:14]=1.[NH2:18][NH2:19].C([C:22](CC)(CC)[C:23]([O-:26])([O-])[O-])C>CO.O.C(OCC)(=O)C>[O:10]([C:13]1[CH2:17][CH2:16][O:15][N:14]=1)[C:6]1[CH:5]=[CH:4][CH:9]=[CH:8][CH:7]=1.[O:26]1[CH:23]=[CH:22][N:19]=[N:18]1

Participants

9

Reactant 4

HCID 9321HydrazineHCID 88068Methyl 3-HydroxybenzoateHCID 139338913-Bromo-1,2-oxazoleHCID 21875354Triethylorthoaceate

Product 2

HCID 10197612OxadiazoleHCID 149604673-Phenoxy-4,5-dihydroisoxazole

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-(phenoxy)-4,5-dihydroisoxazole I-222a and I-222b were prepared in 3 steps according to the following procedures: 3-hydroxy benzoic 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. Triethylorthoacetate (8.0 equiv) is added and the reaction is sealed and heated to reflux for 14 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 ethyl acetate/hexanes) to provide the desired racemic oxadiazole I-222. These compounds can be separated using chiral HPLC methods known in the art. For example, see chiral HPLC Method disclosed herein. [M+H]+=420.5 m/z. Activity: A

Workup

  1. additionis added
  2. concentrationThe reaction mixture is then concentrated under vacuum
  3. customthe reaction is sealed
  4. temperatureheated
  5. temperatureto reflux for 14 h
  6. washThe organic layer was washed water and brine, drive over sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customto provide crude material which
  9. customwas purified

Sources & evidence

ORD record
ord-f536457a541c48679e23dba2d2c8050f
Source dataset
uspto-grants-2015_10
Patent number
US09149465B2

Linked notes

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