Hydroxylamine → (+)-1-[5-(3-Chlorophenyl)-[1,2,4]oxadiazol-3-yl]propan-1-ol

HRID 732115Notes

Reaction equation

HRID 732115 reaction equation
[CH3:1][CH2:2][CH:3]([OH:6])[C:4]#[N:5].O[NH2:8].[Cl:9][C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][CH:18]=1)[C:13](Cl)=[O:14].C([O-])(O)=O.[Na+]>N1C=CC=CC=1>[Cl:9][C:10]1[CH:11]=[C:12]([C:13]2[O:14][N:8]=[C:4]([CH:3]([OH:6])[CH2:2][CH3:1])[N:5]=2)[CH:16]=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 787HydroxylamineHCID 205532-HydroxybutanenitrileHCID 69252Benzoyl chloride, 3-chloro-HCID 516892Sodium Bicarbonate

Product 1

HCID 57837988(+)-1-[5-(3-Chlorophenyl)-[1,2,4]oxadiazol-3-yl]propan-1-olYield 44%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Propionaldehyde cyanohydrin (9.62 g, 113 mmol) was added slowly to hydroxyl amine (100 ml, 1.27 M in EtOH) at 0° C. Stirring was continued at r.t. for 3 h and then the reaction mixture was concentrated to dryness under reduced pressure to give crude (E/Z)-N′,2-dihydroxybutanimidamide (9.1 g, 68%). Crude (E/Z)-N′,2-dihydroxybutanimidamide (8.0 g, 67.7 mmol) was dissolved in pyridine (350 ml) and 3-chlorobenzoyl chloride (8.72 ml, 67.7 mmol) was added slowly at 0° C. After stirring at r.t. for 1 h the mixture was heated at reflux o.n. After cooling to r.t. sat. aq. NaHCO3 was added and the mixture was extracted with DCM. The organic phase was washed with water and brine, dried and concentrated. Column chromatography (hep/EA 4:1) gave 7.15 g (44%) of the title compound. 1H NMR: 1.04 (t, 3 H) 2.00 (m, 2 H) 2.35 (m, 1 H) 4.87 (m, 1 H) 7.47 (t, 1 H) 7.57 (m, 1 H) 8.02 (m, 1 H) 8.14 (m, 1 H)

Workup

  1. concentrationthe reaction mixture was concentrated to dryness under reduced pressure
  2. customto give crude (E/Z)-N′,2-dihydroxybutanimidamide (9.1 g, 68%)
  3. stirringAfter stirring at r.t. for 1 h the mixture
  4. temperaturewas heated
  5. temperatureat reflux o.n
  6. additionwas added
  7. extractionthe mixture was extracted with DCM
  8. washThe organic phase was washed with water and brine
  9. customdried
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-6bcafdf3c03a465f811e3a87e6c96c1c
Source dataset
uspto-grants-2009_09
Patent number
US07585881B2

Reaction notes

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