Triethylamine → 5-Cyclopropyl-3-phenyl-isoxazole-4-carboxylic acid ethyl ester

HRID 731664Notes

Reaction equation

HRID 731664 reaction equation
[OH:1][N:2]=[C:3](Cl)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH2:11]([O:13][C:14](=[O:20])[C:15]#[C:16][CH:17]1[CH2:19][CH2:18]1)[CH3:12].C(N(CC)CC)C>C(OCC)C.C(OC)(C)(C)C.O>[CH2:11]([O:13][C:14]([C:15]1[C:3]([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)=[N:2][O:1][C:16]=1[CH:17]1[CH2:19][CH2:18]1)=[O:20])[CH3:12]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 639964Ethyl 3-cyclopropylprop-2-ynoateHCID 2756315N-hydroxybenzenecarboximidoyl chloride

Product 1

HCID 223090795-Cyclopropyl-3-phenyl-isoxazole-4-carboxylic acid ethyl esterYield 50.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

To a solution of N-hydroxybenzenecarboximidoyl chloride (Tetrahedron Letters, 47(9), 1457-1460, 2006, 500 mg, 3.21 mmol) and cyclopropyl-propynoic acid ethyl ester (Organic Syntheses, 66, 173-179, 1988, 515 mg, 3.21 mmol) in diethyl ether (5 ml) was added dropwise over a period of 2 min at ambient temperature triethylamine (0.54 ml, 3.86 mmol) and the reaction mixture was stirred for 3 d at this temperature. The resulting suspension was diluted with tert-butylmethylether (5 ml) and water (10 ml). The aqueous layer was extracted with tert-butylmethylether (10 ml) and the organic layers were washed with water (10 ml) and brine (10 ml). Drying over sodium sulfate and purification by chromatography (SiO2, heptane:ethyl acetate=98:2 to 80:20) afforded the title compound (414 mg, 50%) as a colorless liquid. MS: m/e=258.1 [M+H]+.

Workup

  1. extractionThe aqueous layer was extracted with tert-butylmethylether (10 ml)
  2. washthe organic layers were washed with water (10 ml) and brine (10 ml)
  3. dry with materialDrying over sodium sulfate and purification by chromatography (SiO2, heptane:ethyl acetate=98:2 to 80:20)

Sources & evidence

ORD record
ord-5626fca0535b4a28b5a8012028cad56a
Source dataset
uspto-grants-2009_09
Patent number
US07585874B2

Reaction notes

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