1,2-Dibromoethane → Methyl 1-(3-methylisoxazol-5-yl)cyclopropanecarboxylate

Into a 15 mL round bottom flask was added methyl 2-(3-methylisoxazol-5-yl)acetate (250 mg, 1.61 mmol) dissolved in N,N-dimethylformamide (7 mL) followed by addition of sodium hydride (60% suspension in mineral oil, 322 mg, 8.06 mmol). The mixture was stirred at room temperature for 15 minutes. 1,2-Dibromoethane (417 μL, 4.83 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 18 h. A saturated aqueous solution of sodium bicarbonate was added to the mixture and it was extracted with dichloromethane (3×). The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in dichloromethane (1.5 mL) and washed (3×) with an aqueous (10%) lithium chloride solution to remove residues of N,N-dimethylformamide. The organics were dried over sodium sulfate, decanted and concentrated under reduced pressure to afford methyl 1-(3-methylisoxazol-5-yl)cyclopropanecarboxylate MS (ES+) (M+H) 182.0; LCMS retention time: 2.53 minutes (Method L). The material was used for the next step without further purification.

1. stirringThe reaction mixture was stirred at room temperature for 18 h
2. extractionwas extracted with dichloromethane (3×)
3. washThe combined organics were washed with brine
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. dissolutionThe residue was dissolved in dichloromethane (1.5 mL)
8. washwashed (3×) with an aqueous (10%) lithium chloride solution
9. customto remove residues of N,N-dimethylformamide
10. dry with materialThe organics were dried over sodium sulfate
11. customdecanted
12. concentrationconcentrated under reduced pressure

ORD record

ord-ed29fe56eda4482289792036b2f06559

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296745B2