Hydrochloric Acid → 5-(1-Methoxy-2-methylpropan-2-yl)-1,2-oxazol-3-amine

Temperatur

100 °C

To a stirred solution of 1.68 g (10.8 mmol) of 5-methoxy-4,4-dimethyl-3-oxo-pentanenitrile and 0.49 g (11.9 mmol) of sodium hydroxide in water (13 mL) is added a solution of 0.98 g (5.9 mmol) of hydroxyamine sulfate in water (4 mL). The reaction mixture is heated to 100° C. for 1.5 h. After this time, the reaction mixture is cooled to room temperature and 0.8 mL (9.7 mmol) of 37% aqueous HCl solution is added. The reaction is heated to 100° C. for 0.5 h. After cooling, the pH of the reaction mixture is adjusted to pH˜12 by addition of 1M aqueous NaOH solution and extracted with DCM (3×20 mL). The organic layers are combined and washed with brine (20 mL), dried over Na2SO4 and filtered. The filtrate is concentrated under reduced pressure. The residual brown oil is purified by column chromatography (Biotage, eluent DCM, MeOH) to yield 0.94 g of 5-(2-methoxy-1,1-dimethyl-ethyl)-isoxazol-3-ylamine as a yellow oil. Yield 51%; m/z 171 [M+H]; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.17 (6H, s), 3.22 (3H, s), 3.26 (2H, s), 5.40 (2H, m) 5.53 (1H, s).

1. temperatureAfter this time, the reaction mixture is cooled to room temperature
2. temperatureThe reaction is heated to 100° C. for 0.5 h
3. temperatureAfter cooling
4. extractionextracted with DCM (3×20 mL)
5. washwashed with brine (20 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationThe filtrate is concentrated under reduced pressure
9. customThe residual brown oil is purified by column chromatography (Biotage, eluent DCM, MeOH)

ORD-Eintrag

ord-069842e9f6be46a991d60afd295e9122

Quelldatensatz

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08048899B2