Triethylamine → Ethyl 3-(4-chlorophenyl)-5-methylisoxazole-4-carboxylate

HRID 2388156Notes

Reaction equation

HRID 2388156 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6](Cl)=[N:7][OH:8])=[CH:4][CH:3]=1.[CH3:12][CH2:13][O:14][C:15](/[CH:17]=[C:18](/N1CCCC1)\[CH3:19])=[O:16].C(N(CC)CC)C>C(O)C>[CH2:13]([O:14][C:15]([C:17]1[C:6]([C:5]2[CH:10]=[CH:11][C:2]([Cl:1])=[CH:3][CH:4]=2)=[N:7][O:8][C:18]=1[CH3:19])=[O:16])[CH3:12]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 736203Ethyl (2E)-3-(1-pyrrolidinyl)-2-butenoateHCID 27555434-chloro-N-hydroxybenzene-1-carbonimidoyl chloride

Product 1

HCID 66643827Ethyl 3-(4-chlorophenyl)-5-methylisoxazole-4-carboxylateYield 69.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a suspension of 4-chloro-N-hydroxy-benzimidoyl chloride (1.11 g, 5.88 mmol) in dry ethanol (9 ml) was added a solution of ethyl (E)-3-(1-pyrrolidino)crotonate (1.08 g, 5.88 mmol) and triethylamine (492 μl, 3.53 mmol) in dry ethanol (9 ml) over a period of twenty minutes at room temperature. The suspension was stirred for eighteen hours before the mixture was concentrated and the residue partitioned between ethyl acetate and water. The organic layer was washed with 0.5 N HCl and brine, before it was dried and concentrated in vacuo. The residue was purified by flash column chromatography with a gradient of ethyl acetate and hexanes on silica gel (40 g) to give the title compound as a white solid (1.09 g): 1H NMR (CDCl3, 200 MHz): δ=7.57 (m, 2H), 7.42 (m, 2H), 4.25 (q, J=7.0 Hz, 2H), 2.74 (s, 3H), 1.27 (t, J=7.0 Hz, 3H); MS: (+) m/z 266.31 (M+1).

Workup

  1. concentrationwas concentrated
  2. customthe residue partitioned between ethyl acetate and water
  3. washThe organic layer was washed with 0.5 N HCl and brine, before it
  4. customwas dried
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography with a gradient of ethyl acetate and hexanes on silica gel (40 g)

Sources & evidence

ORD record
ord-753d507e41a1477485550933038b5b71
Source dataset
uspto-grants-2012_09
Patent number
US08269008B2

Reaction notes

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