反应详情

To a solution of 2-fluoro-6-iodobenzoic acid (15.00 g, 56.39 mmol) in 150 mL CH2Cl2 containing 0.1 mL DMF was added oxalyl chloride (9.30 g, 73.3 mmol) dropwise. The solution was stirred at room temperature for 75 minutes, then concentrated in vacuo. The residue was re-dissolved in 150 mL CH2Cl2, and the solution was saturated three times with ammonia gas. The solution was concentrated in vacuo and dried under vacuum overnight. The residue was dissolved in N,N-dimethylacetamide dimethyl acetal (24.7 mL, 0.169 mol) and heated to 120° C. for 5 hours. Additional N,N-dimethylacetamide dimethyl acetal (25 mL, 0.17 mol) was added over the course of the reaction to drive it to completion. The solution was cooled to room temperature, concentrated in vacuo, and dried under vacuum overnight. To a solution of the intermediate in 57 mL dioxane was added hydroxylamine hydrochloride (4.704 g, 67.69 mmol), 5N NaOH (13.5 mL, 67.7 mmol), and 70% acetic acid (57 mL). The mixture was stirred at 60° C. for 2 hours, then at 90° C. for 3 hours. The resulting solution was cooled to room temperature, diluted with ethyl acetate, and neutralized with aqueous sodium bicarbonate. The organic extract was washed with aqueous sodium bicarbonate and brine, dried over sodium sulfate, filtered and concentrated under vacuum. The residue was filtered through silica gel eluted with 10% ethyl acetate in hexanes to provide 5-(2-fluoro-6-iodophenyl)-3-methyl-1,2,4-oxadiazole as orange yellow crystals that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 305.06 for M+H+.

1. concentrationconcentrated in vacuo
2. dissolutionThe residue was re-dissolved in 150 mL CH2Cl2
3. concentrationThe solution was concentrated in vacuo
4. customdried under vacuum overnight
5. temperatureheated to 120° C. for 5 hours
6. temperatureThe solution was cooled to room temperature
7. concentrationconcentrated in vacuo
8. customdried under vacuum overnight
9. stirringThe mixture was stirred at 60° C. for 2 hours
10. waitat 90° C. for 3 hours
11. temperatureThe resulting solution was cooled to room temperature
12. extractionThe organic extract
13. washwas washed with aqueous sodium bicarbonate and brine
14. dry with materialdried over sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated under vacuum
17. filtrationThe residue was filtered through silica gel
18. washeluted with 10% ethyl acetate in hexanes