Hydrochloric Acid → HCID 56954313, compound

HRID 1050123Notes

Reaction equation

HRID 1050123 reaction equation
Cl.[NH2:2]O.C([O-])(O)=O.[Na+].[F:9][C:10]([F:20])([F:19])[C:11]([CH3:18])([CH3:17])[C:12](=[O:16])[CH2:13][C:14]#[N:15].Cl.[OH-].[Na+]>O.CO>[F:9][C:10]([F:19])([F:20])[C:11]([C:12]1[O:16][N:15]=[C:14]([NH2:2])[CH:13]=1)([CH3:18])[CH3:17]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 569543105,5,5-Trifluoro-4,4-dimethyl-3-oxopentanenitrile

Product 1

HCID 56954313HCID 56954313, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of hydroxylamine hydrochloride (23.2 g, 336 mmol) in water (300 mL) cooled to 0° C. was added NaHCO3 (30 g, 351 mmol) and pH=7.5 adjusted. Then to the mixture was added a solution of 5,5,5-trifluoro-4,4-dimethyl-3-oxopentanenitrile (30 g, 167.4 mmol) in MeOH (40 mL). The mixture was stirred at 65° C. for 15 h. After cooled, the mixture was acidified with conc. HCl to pH=1 and then refluxed for 2 h. After cooling to rt, the mixture was neutralized by 4 M NaOH to pH=8. The mixture was extracted with EA (300 mL×2). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=8:1˜3:1). All fractions found to contain product by TLC (PE/EA=2:1, Rf=0.6) were combined and concentrated to yield a red solid of 5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-amine (19.5 g, 100.5 mmol, 60% yield): 1H NMR (400 MHz, CDCl3) δ 5.79 (s, 1H), 3.96 (s., 2H), 1.53 (s, 6H); ES-LCMS m/z: 195 (M+H).

Workup

  1. temperatureAfter cooled
  2. temperaturerefluxed for 2 h
  3. temperatureAfter cooling to rt
  4. extractionThe mixture was extracted with EA (300 mL×2)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by silica column chromatography (PE/EA=8:1˜3:1)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c397788168fe4905920132a53201caf6
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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