反应详情

温度

-20 °C

A suspension of 60% sodium hydride (749 mg, 18.72 mmole) was washed under argon with hexane (9 ml). The sodium hydride was then cooled to -20° C. and dimethylformamide (20 ml) was added. The mixture was then cooled to -50° C. and methyl bromoacetate (1.77 ml, 18.72 mmole) was added via syringe. Next, a solution of (±)-(cis)-3-azido-4-hydroxymethyl-1-(4-methoxyphenyl)-2-oxoazetidine (3.303 g, 13.37 mmole) in dimethylformamide (25 ml) was added dropwise. The reaction was stirred at -50° C. for ten minutes, warmed to -20° C. over 40 minutes, stirred at this temperature for thirty minutes, and then stirred at -5° C. overnight (ca. sixteen hours). The solvent was mostly removed in vacuo (30° C.). The residue was treated with ether, then pH 4.5 monobasic potassium phosphate buffer. The aqueous layer was extracted with additional ether. The organic extracts were washed with cold 0.5 N hydrochloric acid, water, brine, dried (sodium sulfate), and filtered and concentrated to 4.2 g of an orange oil. The crude product was chromatographed on silica gel (180 g, 230-400 mesh) eluting with 60% hexane-ethyl acetate. Combination of fractions 35-46 (20 ml fractions), concentration and drying in vacuo produced 2.46 g of the title compond as an oil.

1. washwas washed under argon with hexane (9 ml)
2. additiondimethylformamide (20 ml) was added
3. temperatureThe mixture was then cooled to -50° C.
4. temperaturewarmed to -20° C. over 40 minutes
5. stirringstirred at this temperature for thirty minutes
6. stirringstirred at -5° C. overnight (ca. sixteen hours)
7. customThe solvent was mostly removed in vacuo (30° C.)
8. additionThe residue was treated with ether
9. extractionThe aqueous layer was extracted with additional ether
10. washThe organic extracts were washed with cold 0.5 N hydrochloric acid, water, brine
11. dry with materialdried (sodium sulfate)
12. filtrationfiltered
13. concentrationconcentrated to 4.2 g of an orange oil
14. customThe crude product was chromatographed on silica gel (180 g, 230-400 mesh)
15. washeluting with 60% hexane-ethyl acetate
16. concentrationCombination of fractions 35-46 (20 ml fractions), concentration
17. customdrying in vacuo
18. customproduced 2.46 g of the title compond as an oil