Chlorosuccinimide → Ethyl 5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazole-4-carboxylate

HRID 2423424Notes

Reaction equation

HRID 2423424 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:3]=1[CH:4]=[N:5][OH:6].ClN1C(=O)CCC1=O.[CH:20]1([C:23](=O)[CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:22][CH2:21]1.[O-]CC.[Na+]>CN(C)C=O.C1COCC1.O>[CH:20]1([C:23]2[O:6][N:5]=[C:4]([C:3]3[C:2]([Cl:1])=[CH:10][CH:9]=[CH:8][C:7]=3[Cl:11])[C:24]=2[C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:22][CH2:21]1

Participants

8

Reactant 4

HCID 31398ChlorosuccinimideHCID 91328Benzaldehyde, 2,6-dichloro-, oximeHCID 262979Ethyl 3-cyclopropyl-3-oxopropanoateHCID 2723922Sodium ethoxide

Product 1

HCID 52270677Ethyl 5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazole-4-carboxylateYield 8%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent4×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a water bath-cooled solution of 2,6-dichlorobenzaldehyde oxime (2.20 g, 11.6 mmol) in N,N-dimethylformamide (7 mL) was added solid N-chlorosuccinimide (1.55 g, 11.6 mmol). The solutions were stirred while in the water bath for approximately 20 min and the outside the bath for approximately 1 hour. The solution was poured into water and extracted twice with ether. The combined organic layers containing the crude imidoyl chloride were dried over magnesium sulfate and then concentrated. To a separate solution of ethyl 3-cyclopropyl-3-oxopropanoate (2.17 g, 13.9 mmol) in THF (3 mL) at 0° C. was added sodium ethoxide (25 wt % in ethanol, 4.36 mL, 13.9 mmol). The solution was stirred for a few minutes and then the above imidoyl chloride was added. The solution was stirred at 0° C. for 10 minutes and then at ambient temperature overnight. The solution was poured into water and extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, concentrated and purified by chromatography (silica gel, 0-5% ethyl acetate in hexanes gradient elution) to afford ethyl 5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylate (289 mg, 8%). 1H-NMR (400 MHz, DMSO-d6) δ 7.62-7.53 (m, 3H), 4.04 (q, J=7 Hz, 2H), 2.84-2.82 (m, 1H), 1.35-1.25 (m, 4H), 0.93 (t, J=7 Hz, 3H).

Workup

  1. extractionextracted twice with ether
  2. additionThe combined organic layers containing the crude imidoyl chloride
  3. dry with materialwere dried over magnesium sulfate
  4. concentrationconcentrated
  5. stirringThe solution was stirred at 0° C. for 10 minutes
  6. customat ambient temperature
  7. customovernight
  8. extractionextracted three times with ethyl acetate
  9. dry with materialThe combined organic layers were dried over magnesium sulfate
  10. concentrationconcentrated
  11. custompurified by chromatography (silica gel, 0-5% ethyl acetate in hexanes gradient elution)

Sources & evidence

ORD record
ord-7a593f8d09bf4e57b83ce772a74578f6
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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