반응 #557097
ord-64294117f3104c09bcc0121c69b30ff5
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시약
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후처리
- 1온도to cool to ambient temperature
- 2기타The solvent is removed under reduced pressure
- 3기타to give a residue
- 4기타the solvent is removed under reduced pressure
- 5기타to give a residue
실험 절차
Di-tert-butyl (1S,2R,3S,4S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-{[(3,4-difluorophenyl)sulfanyl]methyl}-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylate (4.11 g, 7.19 mmol) is weighed into a one liter round bottom with a stirring bar. Hydrogen chloride (4N in dioxane, 120 mL, 480.0 mmol) is added. The mixture is warmed to 70° C. for 2 hours and then allowed to cool to ambient temperature. The solvent is removed under reduced pressure to give a residue. The residue is dissolve in dichloromethane (200 mL) and the solvent is removed under reduced pressure to give a residue. This is repeated two more times to give (1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid hydrochloride. This material is taken up in tetrahydrofuran (100 mL) as a suspension. To this suspension is added triethylamine (40.08 mL, 287.57 mmol). The suspension is stirred for 10 minutes and then methanol (50 ml) is added. To the reaction is added di-t-butyldicarbonate (4.71 g, 21.57 mmol) and the mixture is heated to 80° C. for 2 hours. The mixture is allowed to come to ambient temperature and the solvent is removed under reduced pressure to give a residue. The residue is dissolved in acetonitrile (50 ml), transferred to a separatory funnel and washed with hexanes. The acetonitrile layer is separated and removed under reduced pressure to give a residue. The residue is suspended in diethyl ether, transferred to a separatory funnel, washed with 1 N aqueous HCl, dried over magnesium sulfate, filtered, and concentrated under reduced pressure giving the title compound (3 g, 6.53 mmol, 90.82% yield). MS (m/z): 457.8 (M−H).