1,4-Diaminocyclohexane → Cis tert-Butyl 4-aminocyclohexylcarbamate

関与物質

反応手順

To a 3 L 3-neck RB flask equipped with a mechanical stirrer, condenser with N2 inlet and temperature probe is added 1,4-diaminocylcohexane P1 (152.2 g, 1332.9 mmol), EtOH (1 L) and t-butyl phenyl carbonate (250 mL, 1351.5 mmol). The reaction mixture is wrapped with Al foil and heated using a heating mantle (JKem temperature controller >2 L setting, Tset=100° C.). A brown solution is obtained and an internal temperature of 73.8° C. is recorded after 2.5 h. After heating for 18 h the now heterogeneous reaction mixture is allowed too cool. The mixture is filtered to remove bis-Boc protected amine, which precipitated as a white solid. The filtrate is concentrated in vacuo to a thick peach colored syrup. The mixture is transferred to an Erlenmeyer flask and the transfer is completed with CH2Cl2 (50 mL). To the mixture H2O (100 mL) is added (pH=9) followed by concentrated HCl (180 mL to pH=2) resulting in the precipitation of the (4-aminocyclohexyl)carbamic acid tert-butyl ester as a hydrochloride salt. The mixture is swirled vigorously until a thick slurry is obtained. Additional CH2Cl2 is added to maximize the amount of precipitate and the slurry is filtered (additional product is obtained from this filtrate #1, as described below). The solid is washed with Et2O (1.4 L). To free-base the HCl salt H2O (500 mL) is added followed by NaOH (2.5N, to pH=12). The mixture is extracted with CH2Cl2 (3×). The combined organic extracts are washed with H2O (3×400 mL), dried over anhydrous Na2SO4 and concentrated in vacuo to give (4-aminocyclohexyl)carbamic acid tert-butyl ester P2a (92.89 g) as a white solid.

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