Chlorosuccinimide → Ethyl 5-cyclobutyl-3-{[(1,1-dimethylethyl)oxy]methyl}-4-isoxazolecarboxylate

HRID 2423452Notes

Reaction equation

HRID 2423452 reaction equation
[CH3:1][C:2]([O:5][CH2:6][CH:7]=[N:8][OH:9])([CH3:4])[CH3:3].ClN1C(=O)CCC1=O.[CH:18]1([C:22](=O)[CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:21][CH2:20][CH2:19]1.[O-]CC.[Na+]>CN(C)C=O.O1CCCC1>[CH:18]1([C:22]2[O:9][N:8]=[C:7]([CH2:6][O:5][C:2]([CH3:4])([CH3:3])[CH3:1])[C:23]=2[C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:19][CH2:20][CH2:21]1

Participants

7

Reactant 4

HCID 31398ChlorosuccinimideHCID 2723922Sodium ethoxideHCID 21846412Ethyl 3-cyclobutyl-3-oxopropanoateHCID 72742322(1,1-Dimethylethyl)oxyethanal oxime

Product 1

HCID 59321584Ethyl 5-cyclobutyl-3-{[(1,1-dimethylethyl)oxy]methyl}-4-isoxazolecarboxylateYield 87%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (1,1-dimethylethyl)oxyethanal oxime (1.71 g, 13.0 mmol) in N,N-dimethylformamide (10 mL) was added N-chlorosuccinimide (1.74 g, 13.0 mmol) while the flask was in a water bath. After approximately 10 minutes the flask was removed from the water bath and the solution was stirred for approximately 1 hour. The solution, containing the crude imidoyl chloride, was then poured into ether and washed twice with water followed by brine, and then was dried over magnesium sulfate and concentrated. Then to a separate solution of ethyl 3-cyclobutyl-3-oxopropanoate (2.66 g, 15.6 mmol) in tetrahydrofuran (8 mL) at 0° C. was added sodium ethoxide (21 wt % solution in ethanol, 5.82 mL, 15.6 mmol). The above imidoyl chloride was diluted with tetrahydrofuran (6 mL) then added to the solution containing the ketoester. A solid was seen to precipitate. After the addition the solution was allowed to warm to ambient temperature and stirred overnight. The mixture was then poured into ether and washed twice with water followed by brine, dried over magnesium sulfate and concentrated to afford ethyl 5-cyclobutyl-3-{[(1,1-dimethylethyl)oxy]methyl}-4-isoxazolecarboxylate (3.13 g, 87%). 1H-NMR (400 MHz, DMSO-d6) δ 4.53 (s, 2H), 4.22 (q, J=7 Hz, 2H), 4.17-4.05 (m, 1H), 2.33-2.27 (m, 4H), 2.09-2.03 (m, 1H), 1.95-1.86 (m, 1H), 1.26 (t, J=7 Hz, 3H), 1.17 (s, 9H).

Workup

  1. customwas in a water bath
  2. customAfter approximately 10 minutes the flask was removed from the water bath
  3. additionThe solution, containing the crude imidoyl chloride
  4. additionwas then poured into ether
  5. washwashed twice with water
  6. dry with materialwas dried over magnesium sulfate
  7. concentrationconcentrated
  8. additionthen added to the solution
  9. customto precipitate
  10. additionAfter the addition the solution
  11. stirringstirred overnight
  12. additionThe mixture was then poured into ether
  13. washwashed twice with water
  14. dry with materialdried over magnesium sulfate
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-4bbcefd7ad974e3b8d62c12db273f15d
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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