ETHYL5-TERT-BUTYLISOXAZOLE-3-CARBOXYLATE

Synthesis of 5-tert-butyl-isoxazole-3-carboxylic acid ethyl ester (54) A solution of tert-butyl-enone (50) (6.00 g, 30.0 mmol) in anhydrous ethanol/THF (1:1) (70 mL) was stirred at room temperature. To this solution was added hydroxylamine hydrochloride (2.29 g, 33.0 mmol) and the resulting mixture was stirred 12 h under nitrogen. The mixture was then heated to reflux with a soxlet filled with molecular sieves during 2 h. The mixture was allowed to cool down and the solvent was evaporated. Water (100 mL) was added and the mixture was extracted with dichloromethane (2.x.100 mL). The organic extracts were combined, dried with sodium sulfate, and concentrated. The crude product was purified by silica gel chromatography to give 5-tert-butyl-isoxazole-3-carboxylic acid ethyl ester (54) as a colorless oil (3 g, 51percent). 54: A solution of tert-butyl-enone (50) (6.00 g, 30.0 mmol) in anhydrous ethanol/THF (1:1) (70 mL) was stirred at room temperature. To this solution was added hydroxylamine hydrochloride (2.29 g, 33.0 mmol) and the resulting mixture was stirred for 12 h under nitrogen. The mixture was then heated to reflux with a soxlet filled with molecular sieves during 2 h. The mixture was allowed to cool down and the solvent was evaporated. Water (100 mL) was added and the mixture was extracted with dichloromethane (2.x.100 mL). The organic extracts were combined, dried with sodium sulfate, and concentrated. The crude product was purified by silica gel chromatography to give 5-tert-butyl-isoxazole-3-carboxylic acid ethyl ester (54) as a colorless oil (3 g, 51percent). 54: The title compound is prepared by those skilled in the art according to a literature procedure (Lepage et al, Eur. J. Med. Chem., 1992, 27, 6, 581-93).To a solution of sodium hydrogen carbonate (2.10 g, 25 mmol) and hydroxylamine hydrochloride (1.73 g, 25 mmol) in ethanol (25 mL) is added ethyl trimethyl acetopyruvate (5.00 g, 25 mmol). The mixture is heated at reflux for 16 h. After this time the sodium chloride is removed by filtration and the filtrate is concentrated under reduced pressure. The residue is purified by chromatography on silica eluting with 8/2 cyclohexane/ethyl acetate to provide the title compound as a yellow oil (3.2 g, 65percent), m/z 198 [M+HStep 1: Synthesis of 5-tert-butyl-isoxazole-3-carboxylic acid ethyl ester The title compound is prepared by those skilled in the art according to a literature procedure (Lepage et al, Eur. J. Med. Chem., 1992, 27, 6, 581-93). To a solution of sodium hydrogen carbonate (2.10 g, 25 mmol) and hydroxylamine hydrochloride (1.73 g, 25 mmol) in ethanol (25 mL) is added ethyl trimethyl acetopyruvate (5.00 g, 25 mmol). The mixture is heated at reflux for 16 h. After this time the sodium chloride is removed by filtration and the filtrate is concentrated under reduced pressure. The residue is purified by chromatography on silica eluting with 8/2 cyclohexane/ethyl acetate to provide the title compound as a yellow oil (3.2 g, 65percent), m/z 198 [M+H

Molecular Weight:197.23
XLogP3:2.6
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:4
Exact Mass:197.10519334
Monoisotopic Mass:197.10519334
Topological Polar Surface Area:52.3
Heavy Atom Count:14
Complexity:210
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes