ClC(OCC)=O.[C:7]([O:11][C:12]([NH:14][C@H:15]1[CH2:20][O:19][C@H:18]([C:21]([OH:23])=O)[CH2:17][CH2:16]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].C(N(C(C)C)CC)(C)C.[N+:33](=[CH2:35])=[N-:34].Cl>O1CCCC1.C(OCC)(=O)C>[C:7]([O:11][C:12](=[O:13])[NH:14][C@@H:15]1[CH2:16][CH2:17][C@@H:18]([C:21](=[O:23])[CH:35]=[N+:33]=[N-:34])[O:19][CH2:20]1)([CH3:8])([CH3:9])[CH3:10]Ethyl chloroformate (605 μL, 6.36 mmol, 1.2 eq) is added dropwise at 0° C. to a stirred solution of (2S,5R)-5-tert-butoxycarbonylamino-tetrahydro-pyran-2-carboxylic acid (1.3 g, 5.30 mmol, 1.0 eq) and diisopropylethylamine (1.38 mL, 7.95 mmol, 1.5 eq) in tetrahydrofuran (50 mL). After 30 minutes stirring at room temperature the reaction mixture is cooled down to −20° C. before the addition of diazomethane (2.0 M solution in diethyl ether, 26.5 mL, 53.0 mmol, 10.0 eq). After 15 hours stirring at −20° C., the reaction mixture is carefully acidified to pH 6 with 1.0 N hydrochloric acid aqueous solution and then extracted with ethyl acetate (3×30 mL). The combined organic layers are washed with brine, dried over sodium sulfate, filtered and concentrated to give a crude product that is purified by column chromatography (silica gel, eluent: petroleum ether:ethyl acetate, 10:1 to 3:1, v/v) to afford (3R,6S)-[6-(2-diazo-acetyl)-tetrahydro-pyran-3-yl]-carbamic acid tert-butyl ester as a white solid (1.14 g, 80% yield).
Loading…
