5-Isoxazolecarboxylic acid, 3-(1,1-dimethylethyl)-, methyl ester synthesis

5synthesis methods

Product Name:5-Isoxazolecarboxylic acid, 3-(1,1-dimethylethyl)-, methyl ester
CAS Number:133674-39-2
Molecular formula:C9H13NO3
Molecular Weight:183.2

630-19-3 Synthesis

630-19-3
308 suppliers
$13.00/1g

922-67-8 Synthesis

922-67-8
341 suppliers
$6.00/1g

5-Isoxazolecarboxylic acid, 3-(1,1-dimethylethyl)-, methyl ester

133674-39-2
21 suppliers
$45.00/50mg

Yield: 28%

Reaction Conditions:

Stage #1:pivalaldehyde with hydroxylamine hydrochloride;sodium hydroxide in water;tert-butyl alcohol at 20; for 0.5 h;
Stage #2:propynoic acid methyl ester with chloroamine-T;copper;copper(II) sulfate in water;tert-butyl alcohol at 20;Reflux;

Steps:

D-1.1
The title compound is prepared from commercially available materials by those skilled in the art by adaptation of a literature reference (Hansen et al, J. Org. Chem., 2005, 70, 19, 7761-4). To a solution of pivaldehyde (10.09 g, 117 mmol) in 1:1 tert-butanol/water (400 niL) are added hydroxylamine hydrochloride (8.13 g, 117 mmol) and sodium hydroxide (4.70 g, 117 mmol). The solution is stirred at room temperature for 30 min before chloramine-T trihydrate (54.49 g, 234 mmol) is added in portions over 5 min followed by copper sulfate (3.27 g, 13 mmol), copper powder (0.75 g, 12 mmol) and methyl propiolate (10.4 mL, 9.84 g, 117 mmol). The reaction mixture is heated at reflux where it is maintained for 2 h. After this time, the mixture is cooled to room temperature and poured onto ice/water (500 g). Ammonium hydroxide (100 mL) is added and the solution is extracted with dichloromethane (3 x 200 mL). The organic layers are combined, dried (Na₂SO₄), filtered and concentrated under reduced pressure. The solid is suspended in heptane (3 x 500 mL), filtered and the combined filtrates are concentrated under reduced pressure. The residue is purified by chromatography on silica eluting with 9/1 heptane/ethyl acetate to afford the title compound as a yellow oil (5.97 g, 28%), m/z 184 [M+H⁺]. ¹U NMR (400 MHz, CHLOROFORM-d) δ ppm 1.36 (9 H, s), 3.96 (3 H, s), 6.88 (1 H, s).

References:

BOEHRINGER INGELHEIM INTERNATIONAL GMBH;BOEHRINGER INGELHEIM PHARMA GMBH & CO. KG WO2009/140089, 2009, A2 Location in patent:Page/Page column 47-48

554-12-1 Synthesis