Acetic Acid → HCID 21251137, compound

3-Ethoxy-4-methylisoxazole-5-carbonitrile (2.6 g, 17.1 mmol), 5.4 M NaOMe in MeOH (0.6 mL, 3.4 mmol) and EtOH (80 mL) was stirred at room temperature for 30 min. Acetic acid (2.2 mL, 39.3 mmol) and 2-amino-2-methylpropan-1-ol (1.8 mL, 18.8 mmol) were added, and the resulting mixture was boiled under reflux for 20 h. The reaction mixture was cooled, added water (100 mL) and extracted with EtOAc (3×100 mL). The organic extracts were washed with 1 M NaOH (50 mL), brine, dried (MgSO4) and evaporated in vacuo. The residue was dissolved in EtOH (60 mL), a solution of KOH (1.8 g, 32 mmol) in water (12 mL) was added, and the mixture was stirred at room temperature for 20 h. EtOH was removed in vacuo, water was added (80 mL) and the aqueous phase extracted with EtOAc (3×100 mL). The organic extracts were washed with brine, dried (MgSO4) and evaporated in vacuo. Flash chromatography (silica gel, eluent: EtOAc/heptane/triethylamine=75:25:1) gave crude title compound as a yellow oil (2.0 g, 52%).

1. temperatureunder reflux for 20 h
2. temperatureThe reaction mixture was cooled
3. extractionextracted with EtOAc (3×100 mL)
4. washThe organic extracts were washed with 1 M NaOH (50 mL), brine
5. dry with materialdried (MgSO4)
6. customevaporated in vacuo
7. dissolutionThe residue was dissolved in EtOH (60 mL)
8. customEtOH was removed in vacuo, water
9. additionwas added (80 mL)
10. extractionthe aqueous phase extracted with EtOAc (3×100 mL)
11. washThe organic extracts were washed with brine
12. dry with materialdried (MgSO4)
13. customevaporated in vacuo

ORD record

ord-0e5c8d596fc84607891526ab4678cbf4

Source dataset

uspto-grants-2001_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06200999B1