Chlorosuccinimide → Ethyl 5-cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylate

HRID 2423412ノート

反応式

HRID 2423412 の反応式
[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:24](=O)[CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:23][CH2:22][CH2:21]1.[O-]CC.[Na+]>CN(C)C=O.C1COCC1.O>[CH:20]1([C:24]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:25]=2[C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:21][CH2:22][CH2:23]1

参加物

8

反応物 4

HCID 31398ChlorosuccinimideHCID 91328Benzaldehyde, 2,6-dichloro-, oximeHCID 2723922Sodium ethoxideHCID 21846412Ethyl 3-cyclobutyl-3-oxopropanoate

生成物 1

HCID 59264874Ethyl 5-cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylate収率 38.5%

試薬・触媒・溶媒 3

HCID 962Water溶媒4 回HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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 solution was stirred while in the water bath for approximately 20 min and outside the bath for approximately 1 hr. 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-cyclobutyl-3-oxopropanoate (2.37 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-cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylate (1.52 g, 38%). 1H-NMR (400 MHz, DMSO-d6) δ 7.63-7.53 (m, 3H), 4.29-4.20 (m, 1H), 4.02 (q, J=7 Hz, 2H), 2.43-2.36 (m, 4H), 2.15-2.06 (m, 1H), 1.97-1.89 (m, 1H), 0.94 (t, J=7 Hz, 3H).

後処理

  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)

出典と根拠

ORDレコード
ord-26c027b0ec8e4e3082fd9c17339de49f
出典データセット
uspto-grants-2011_06
特許番号
US07960552B2

反応ノート

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