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

HRID 2219403Notes

Reaction equation

HRID 2219403 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, 2006, 47, 1457, 2006; 500 mg, 3.21 mmol) and cyclopropyl-propynoic acid ethyl ester (Organic Syntheses, 1988, 66, 173; 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-8c1b2b5070184b5697b16403969f7f74
Source dataset
uspto-grants-2008_08
Patent number
US07414061B2

Reaction notes

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