Methyl iodide → 3-(2-(N-tert-Butoxycarbonylamino)ethoxy)-4-methyl-5-phenylisoxazole

HRID 612870Notes

Reaction equation

HRID 612870 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][O:11][C:12]1[CH:16]=[C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:14][N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:23]([Li])CCC.CCCCCC.CI.P([O-])(O)(O)=O.[K+]>O1CCCC1>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][O:11][C:12]1[C:16]([CH3:23])=[C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:14][N:13]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 516951Monobasic potassium phosphateHCID 154349603-(2-(N-tert-butoxycarbonylamino)ethoxy)-5-phenylisoxazoleHCID 178418244HCID 178418244, compound

Product 1

HCID 195966953-(2-(N-tert-Butoxycarbonylamino)ethoxy)-4-methyl-5-phenylisoxazoleYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

3-(2-(N-tert-Butoxycarbonylamino)ethoxy)-5-phenylisoxazole (0.30 g) was dissolved in tetrahydrofuran (10 ml), and a solution of n-butyllithium/n-hexane (1.56M, 1.4 ml) was added dropwise thereto at -70° C. under a nitrogen atmosphere, followed by stirring of the resulting mixture for 10 minutes. Then, methyl iodide (0.09 ml) was added dropwise to the reaction mixture, and the resulting mixture was stirred for 10 minutes. After the temperature of the reaction mixture was raised to 0° C., the reaction mixture was poured into ice-cold water, and an aqueous potassium dihydrogenphosphate solution was added to the mixture to adjust the pH to a value of 6. Then, the mixture was extracted with ethyl acetate and the organic layer was washed with a saturated aqueous NaCl solution, followed by drying over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=4/1) to obtain the title compound (0.29 g, 94%) as a colorless powder.

Workup

  1. customat -70° C.
  2. stirringthe resulting mixture was stirred for 10 minutes
  3. additionthe reaction mixture was poured into ice-cold water
  4. extractionThen, the mixture was extracted with ethyl acetate
  5. washthe organic layer was washed with a saturated aqueous NaCl solution
  6. dry with materialby drying over anhydrous magnesium sulfate
  7. filtrationAfter filtration
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=4/1)

Sources & evidence

ORD record
ord-e42af05582f0440fa4024d9c88d3d1ad
Source dataset
uspto-grants-1999_12
Patent number
US06005116

Reaction notes

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