Cyanoacetic acid → 3-(5-Methyl-3-phenyl-isoxazol-4-yl)-3-oxo-propionitrile

HRID 2120858Notes

Reaction equation

HRID 2120858 reaction equation
[C:1]([CH2:3][C:4]([OH:6])=O)#[N:2].C([Li])CCC.[CH3:12][C:13]1[O:17][N:16]=[C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:14]=1C(Cl)=O>C1COCC1>[CH3:12][C:13]1[O:17][N:16]=[C:15]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:14]=1[C:4](=[O:6])[CH2:3][C:1]#[N:2]

Participants

5

Reactant 3

HCID 9740Cyanoacetic acidHCID 856245-Methyl-3-phenylisoxazole-4-carbonyl chlorideHCID 178418339Butyllithium

Product 1

HCID 234356403-(5-Methyl-3-phenyl-isoxazol-4-yl)-3-oxo-propionitrileYield 67.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To cyanoacetic acid (0.43 g, 5.12 mmol) in THF at −78° C., containing one crystal of 1,1′-bipyridyl was added n-butyl lithium (6.4 mL, 10.24 mmol). The temperature was allowed to warm to 0° C. resulting in a pink colored solution. After cooling to −78° C., 5-Methyl-3-phenyl-isoxazole-4-carbonyl chloride (0.567 g, 2.56 mmol) in THF (5 mL) was added dropwise. The mixture was stirred at −78° C. for 1 hr. and at ambient temperature for an addition 1 hr. The reaction was quenched with 1N HCl (13 mL0 and extracted twice with CH2Cl2. Combined extracts were washed with saturated NaHCO3, brine, dried over MgSO4 to give the title compound (0.391 g, 67% yield).

Workup

  1. customresulting in a pink colored solution
  2. temperatureAfter cooling to −78° C.
  3. additionand at ambient temperature for an addition 1 hr
  4. customThe reaction was quenched with 1N HCl (13 mL0
  5. extractionextracted twice with CH2Cl2
  6. washCombined extracts were washed with saturated NaHCO3, brine
  7. dry with materialdried over MgSO4

Sources & evidence

ORD record
ord-c1620de8258e4ddeb2bfa1879a5170b1
Source dataset
uspto-grants-2004_02
Patent number
US06693108B2

Reaction notes

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