반응 #557093

반응 방정식

S-(−)-2-methyl-CBS-oxazaborolidine

4-fluoro-3-methyl-benzenethiol

triethylamine

Di-tert-butyl (1S,2R,5R,6R)-2-(tert-butoxycarbonylamino)-3-methylene-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylate

borane methyl sulfide

→

title compound

수율 91.5%

Di-tert-butyl (1S,2R,3S,4R,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-{[(4-fluoro-3-methyl-phenyl)sulfanyl]methyl}-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylate

수율 91.5%

용매

ether

diethyl ether

반응 조건

후처리

1. 1
   온도to cool to ambient temperature
2. 2
   workup.ADDITIONtransferred to addition funnel
3. 3
   workup.STIRRINGThe mixture is stirred for an additional hour after final
4. 4
   workup.ADDITIONaddition
5. 5
   workup.ADDITIONSilica gel (40 g) is added over 30 minutes
6. 6
   온도the reaction mixture is gradually warmed to ambient temperature
7. 7
   여과The suspension is filtered
8. 8
   세척washed with 300 ml of diethyl ether
9. 9
   농축The solvent is concentrated under reduced pressure
10. 10
    기타giving a residue
11. 11
    기타The residue is purified by flash chromatography
12. 12
    세척eluting with (0 to 25% ethyl acetate/hexanes)

실험 절차

Di-tert-butyl (1S,2R,5R,6R)-2-(tert-butoxycarbonylamino)-3-methylene-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylate (8 g, 18.9 mmol) in diethyl ether (80 mL) is bubbled with nitrogen gas for 10 minutes. 4-fluoro-3-methyl-benzenethiol (2.7 g, 18.9 mmol) and triethylamine (0.26 mL, 1.89 mmol) are added. The mixture is warmed to 40° C. and stirred for 15 minutes. The mixture is then allowed to cool to ambient temperature, transferred to addition funnel and added slowly over 2 hours to a 200 ml ether solution at −10° C. which contains S-(−)-2-methyl-CBS-oxazaborolidine (1M in tetrahydrofuran) (5.67 mL, 5.67 mmol) and borane-methyl sulfide complex (2M in tetrahydrofuran, 8.5 mL, 17 mmol). The mixture is stirred for an additional hour after final addition. Silica gel (40 g) is added over 30 minutes and the reaction mixture is gradually warmed to ambient temperature. The suspension is filtered, and washed with 300 ml of diethyl ether. The solvent is concentrated under reduced pressure giving a residue. The residue is purified by flash chromatography, eluting with (0 to 25% ethyl acetate/hexanes) to give the title compound (9.8 g, 17.3 mmol, 91.5% yield). MS (m/z): 565.8 (M−H).

출처