반응 #2260175

반응 방정식

HCl

potassium t-butoxide

di-tert-butyl (1R,2R,3S,4S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-(1H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylate

methyl iodide

→

title compound

수율 26.0%

Di-tert-butyl (1R,2R,3 S,4S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-[(1-methyl-1,2,4-triazol-3-yl)sulfanyl]bicyclo[3.1.0]hexane-2,6-dicarboxylate

수율 26.0%

용매

water

tetrahydrofuran

반응 조건

후처리

1. 1
   온도Allow the mixture to warm to room temperature
2. 2
   workup.STIRRINGstir for 30 minutes at room temperature
3. 3
   workup.ADDITIONPour crude
4. 4
   추출extract into ethyl acetate
5. 5
   건조Dry the organic layer over magnesium sulfate
6. 6
   여과filter
7. 7
   농축concentrate under reduced pressure
8. 8
   기타Purify by reverse phase flash chromatography (100 g C18 column
9. 9
   세척eluting with 45-95% Acetonitrile/Water (with 0.1% trifluoroacetic acid in both), compound elutes at 89% Acetonitrile)
10. 10
    추출Extract with ethyl acetate
11. 11
    건조dry the organic layer over magnesium sulfate
12. 12
    여과filter
13. 13
    농축concentrate under reduced pressure

실험 절차

Dissolve di-tert-butyl (1R,2R,3S,4S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-(1H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylate (0.60 g, 0.893 mmol) in anhydrous tetrahydrofuran (3.6 mL) in a flame-dried flask and cool to −78° C. Add potassium t-butoxide (0.80 g, 0.893 mmol) and stir for 15 minutes. Add methyl iodide (0.127 g, 0.893 mmol, pretreated by filtration through basic alumina) and allow to stir at −78° C. for 15 minutes. Allow the mixture to warm to room temperature and then stir for 30 minutes at room temperature. Pour crude reaction mixture into water and adjust pH to 6 with 1N aqueous HCl and extract into ethyl acetate. Dry the organic layer over magnesium sulfate, filter and concentrate under reduced pressure. Purify by reverse phase flash chromatography (100 g C18 column eluting with 45-95% Acetonitrile/Water (with 0.1% trifluoroacetic acid in both), compound elutes at 89% Acetonitrile). Combine the desired fractions and neutralize with aqueous bicarbonate. Extract with ethyl acetate, dry the organic layer over magnesium sulfate, filter and concentrate under reduced pressure to yield the title compound as a white foam (0.16 g, 0.23 mmol, 26%): MS (m/z): 473/475/477 (M+1).

출처