Ethanol → Ethyl 5-cyclopentyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylate

HRID 2423408Notes

Reaction equation

HRID 2423408 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:25](=O)[CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:24][CH2:23][CH2:22][CH2:21]1.[O-]CC.[Na+].C(O)C>CN(C)C=O.O1CCCC1.O>[CH:20]1([C:25]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:26]=2[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

9

Reactant 5

HCID 702EthanolHCID 31398ChlorosuccinimideHCID 91328Benzaldehyde, 2,6-dichloro-, oximeHCID 2723922Sodium ethoxideHCID 11159709Ethyl 3-cyclopentyl-3-oxopropanoate

Product 1

HCID 59321583Ethyl 5-cyclopentyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylateYield 43.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2,6-dichlorobenzaldehyde oxime (3.73 g, 19.6 mmol) in N,N-dimethylformamide (12 mL) was added solid N-chlorosuccinimide (2.62 g, 19.6 mmol). The solution was stirred for approximately 1 hour and the poured into water and extracted twice with ether. The combined organic layers containing the crude imidoyl chloride were dried over magnesium sulfate and concentrated. To a solution of ethyl 3-cyclopentyl-3-oxopropanoate (4.34 g, 23.6 mmol) in tetrahydrofuran (5 mL) at 0° C. was added a 25 wt % solution of sodium ethoxide in ethanol (7.4 mL, 24 mmol) quickly. The above imidoyl chloride was added. A solid was seen to precipitate. The mixture was allowed to warm to ambient temperature and stir overnight. The mixture was then poured into water and extracted three times with ethyl acetate and the combined organic layers were dried over magnesium sulfate, concentrated and the residue purified by chromatography (silica gel 5% ethyl acetate in hexanes) to afford ethyl 5-cyclopentyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylate (3.04 g, 43%). 1H-NMR (400 MHz, DMSO-d6) δ 7.63-7.53 (m, 3H), 4.02 (q, J=7 Hz, 2H), 3.92-3.84 (m, 1H), 2.14-2.06 (m, 2H), 1.84-1.64 (m, 6H), 0.91 (t, J=5 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. customto precipitate
  6. stirringstir overnight
  7. additionThe mixture was then poured into water
  8. extractionextracted three times with ethyl acetate
  9. dry with materialthe combined organic layers were dried over magnesium sulfate
  10. concentrationconcentrated
  11. customthe residue purified by chromatography (silica gel 5% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-0ae41109db4a4270b45c1aac40e72fd3
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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