Hydrochloric Acid → 3-Isoxazolamine, 5-(1,1-dimethylethyl)-

HRID 128432Notes

Reaction equation

HRID 128432 reaction equation
[C:1]([CH2:7][C:8]#[N:9])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[OH-].[Li+].Cl.[NH2:13]O.Cl>C(O)C.O>[NH2:9][C:8]1[CH:7]=[C:1]([C:2]([CH3:5])([CH3:4])[CH3:3])[O:6][N:13]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 108871Pentanenitrile, 4,4-dimethyl-3-oxo-HCID 443297Hydroxyamine hydrochloride

Product 1

HCID 1714733-Isoxazolamine, 5-(1,1-dimethylethyl)-Yield 52%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

In a 1 l. 3-neck round bottom flask there was placed 30 g. of pivalyl acetonitrile, 13.5 g. of lithium hydroxide, 394 ml. of water and 281 ml. of ethanol. This mixture was heated to reflux and there was added thereto over a period of 10 minutes 94 ml. of an aqueous solution of 22.2 g. of hydroxylamine hydrochloride. The pH of the reaction mixture after the addition was complete was about 7.3. This pH was adjusted to about pH 6.7 using concentrated aqueous hydrochloric acid. After 30 minutes the pH was about 6.1. After 1 hour the pH was about 6.3. The pH was checked again at 2 hours and at 3 hours after the addition was complete and the pH at those times was about 6.6. A recheck of the pH at 4 hours, 5 hours, and 6 hours revealed the pH to be at about 6.7. The reaction mixture was then refluxed overnight. The following morning the pH was about 6.8. The reaction mixture was cooled and the ethanol removed from the mixture on the rotovapor at room temperature. A solid which separated was filtered off and dried. It weighed 18.65 g. and it was determined by vpc that the product contained 97% of the desired 3-amino-5-(t-butyl)isoxazole, and 1.6% of 5-amino-3-(t-butyl)isoxazole. Yield: 52% of desired isomer.

Workup

  1. temperatureThis mixture was heated
  2. temperatureto reflux
  3. additionthere was added
  4. additionThe pH of the reaction mixture after the addition
  5. waitAfter 30 minutes the pH was about 6.1
  6. waitAfter 1 hour the pH was about 6.3
  7. waitThe pH was checked again at 2 hours and at 3 hours
  8. additionafter the addition
  9. waitA recheck of the pH at 4 hours
  10. custom5 hours, and 6 hours
  11. temperatureThe reaction mixture was then refluxed overnight
  12. temperatureThe reaction mixture was cooled
  13. customthe ethanol removed from the mixture on the rotovapor at room temperature
  14. customA solid which separated
  15. filtrationwas filtered off
  16. customdried

Sources & evidence

ORD record
ord-bff11fe04a2b4d3aa37a8e46c9b7be8f
Source dataset
uspto-grants-1981_03
Patent number
US04259501

Reaction notes

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