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

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.

1. customTo a 3 L 3-neck RB flask equipped with a mechanical stirrer, condenser with N2 inlet
2. temperatureheated
3. customa heating mantle (JKem temperature controller >2 L setting, Tset=100° C.)
4. customA brown solution is obtained
5. temperatureAfter heating for 18 h the now heterogeneous reaction mixture
6. temperatureis allowed too cool
7. filtrationThe mixture is filtered
8. customto remove bis-Boc
9. customprecipitated as a white solid
10. concentrationThe filtrate is concentrated in vacuo to a thick peach colored syrup
11. additionTo the mixture H2O (100 mL) is added (pH=9)

ORD record

ord-b7825b183c5042e1ad2e730f28f8af22

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08273747B2