反应详情

温度

10 °C

Add bromine (114; mL, 2.2; mol) dropwise over 45; min to a cooled aqueous solution of sodium hydroxide (4.6M, 3.84; L, 17.8; mol) at −10° C. and stir for 0.5; hour to give a yellow solution. Add this solution dropwise to a pre-cooled −5° C. solution of (1R,2R)-2-methyl-cyclopropanecarboxylic acid (4-acetyl-3-bromo-isothiazol-5-yl)-amide (150; g, 495; mmol) in 1,4-dioxane (2; L) and stir 45; min at 5-10° C. Maintain cooling at 10° C. whilst adding a 40% (wt/wt) aqueous solution of sodium bisulfite (47.5; mL) over 5 min, stir 5; min and add slowly 12; M hydrochloric acid (approximately 500; mL) over 15 min until acidic (pH=2). Dilute with ethyl acetate (2; L) and separate the layers. Extract the aqueous layer twice with ethyl acetate (1; L). Combine the organic phases, dry over magnesium sulfate, filter and concentrate. Dissolve the residue in dichloromethane (600 mL), dilute with n-hexane (3; L), and cool to 5° C. overnight. Filter and wash the recovered solid with four portions of n-hexane (125; mL) to give the title compound as a white solid (92.6; g, 55%). If desired a second crop of the title compound (50.97; g, 30%) can be harvested from the mother liquors. MS (m/z): 339, 341, 343; (M+1).

1. customhour to give a yellow solution
2. customat 5-10° C
3. temperatureMaintain
4. stirringstir 5
5. additionmin and add slowly 12
6. customseparate the layers
7. extractionExtract the aqueous layer twice with ethyl acetate (1; L)
8. dry with materialCombine the organic phases, dry over magnesium sulfate
9. filtrationfilter
10. concentrationconcentrate
11. dissolutionDissolve the residue in dichloromethane (600 mL)
12. additiondilute with n-hexane (3; L)
13. temperaturecool to 5° C. overnight
14. filtrationFilter
15. washwash the recovered solid with four portions of n-hexane (125; mL)