Hydrochloric Acid → 5-Methyl-1,2-benzoxazol-3-amine

To a solution of 1 M potassium tert-butoxide in THF (40.7 mL, 40.7 mmol) was added acetone oxime (2.97 g, 40.7 mmol) in one portion. After stirring for 20 min at rt, a solution of 2-fluoro-5-methylbenzonitrile (5.0 g, 37.0 mmol) in THF (30 mL) was slowly added from an addition funnel. After stirring for 3 hrs at room temperature, the mixture was heated at 60° C. overnight. A dark brown solution was obtained. The reaction was quenched with water (10 mL). The reaction mixture was partitioned between saturated NaHCO3 solution (50 mL) and ethyl acetate (150 mL). The organic layer was separated and washed with water (3×30 mL) and the solvent was removed on a rotary evaporator to yield a brown solid. The solid was then treated with a mixture of EtOH (80 mL), H2O (53 mL) and HCl (12 N, 26.8 mL) at reflux for 2 hrs. After cooling, the reaction mixture was basified with solid sodium carbonate and NaOH (1 N, 30 mL). The reaction mixture was then extracted with ethyl acetate (2×100 mL). The organic layer was washed with water (2×30 mL) and brine (40 mL), then dried over anhydrous sodium sulfate. Rotary evaporation of solvent afforded a brown solid (4.6 g). LC/MS (ESI) (M+H++CH3CN: 190.0). This product was used without further purification.

1. stirringAfter stirring for 3 hrs at room temperature
2. temperaturethe mixture was heated at 60° C. overnight
3. customA dark brown solution was obtained
4. customThe reaction was quenched with water (10 mL)
5. customThe reaction mixture was partitioned between saturated NaHCO3 solution (50 mL) and ethyl acetate (150 mL)
6. customThe organic layer was separated
7. washwashed with water (3×30 mL)
8. customthe solvent was removed on a rotary evaporator
9. customto yield a brown solid
10. temperatureat reflux for 2 hrs
11. temperatureAfter cooling
12. extractionThe reaction mixture was then extracted with ethyl acetate (2×100 mL)
13. washThe organic layer was washed with water (2×30 mL) and brine (40 mL)
14. dry with materialdried over anhydrous sodium sulfate
15. customRotary evaporation of solvent

ORD-Eintrag

ord-114f3aed530b412f9111df58a87e4150

Quelldatensatz

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07829584B2