Triethylamine → 3-(2-Chloro-pyridin-3-yl)-5-methyl-isoxazole-4-carboxylic acid methyl ester

HRID 1823265Notes

Reaction equation

HRID 1823265 reaction equation
Cl[C:2]([C:5]1[C:6]([Cl:11])=[N:7][CH:8]=[CH:9][CH:10]=1)=[N:3][OH:4].[CH3:12][O:13][C:14](=[O:18])[C:15]#[C:16][CH3:17].C(N(CC)CC)C>C(OCC)C>[CH3:12][O:13][C:14]([C:15]1[C:2]([C:5]2[C:6]([Cl:11])=[N:7][CH:8]=[CH:9][CH:10]=2)=[N:3][O:4][C:16]=1[CH3:17])=[O:18]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 141019Methyl but-2-ynoateHCID 73867584Chloro(2-chloro(3-pyridyl))(hydroxyimino)methane

Product 1

HCID 574254353-(2-Chloro-pyridin-3-yl)-5-methyl-isoxazole-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

Combine chloro(2-chloro(3-pyridyl))(hydroxyimino)methane (2.90 g, 0.015 mol) with methyl-2-butynoate (1.19 mL, 0.012 mol) in diethyl ether (75 mL). Cool the mixture in an ice bath under a nitrogen atmosphere. Add a solution of triethylamine (1.77 mL, 0.013 mol) in diethyl ether (10 mL) in a dropwise manner. Stir the mixture overnight while warming to ambient temperature. Quench the mixture with water and extract with diethyl ether. Concentrate the combined extracts and elute over silica gel with 10% methanol/dichloromethane to give the desired isoxazole along with a co-eluting impurity (2.30 g, 60%). MS(ES): (M+1)+ 253.0, 255.0 m/z.

Workup

  1. temperatureCool the mixture in an ice bath under a nitrogen atmosphere
  2. customQuench the mixture with water
  3. extractionextract with diethyl ether
  4. concentrationConcentrate the combined extracts
  5. washelute over silica gel with 10% methanol/dichloromethane

Sources & evidence

ORD record
ord-57b8b9343a5341c3b83b69c8b00a2e28
Source dataset
uspto-grants-2006_05
Patent number
US07037921B2

Reaction notes

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