Benzyl Chloride → (1S,3R)-3-(dibenzylamino)cyclohexanol

Temperature

75 °C

To a suspension of (1S,3R)-3-aminocyclohexanol (5 g, 43.4 mmol; prepared as described in Tetrahedron: Asymmetry 15: 2051-2056 (2004)) and sodium bicarbonate (12.03 g, 143 mmol) in ethanol (100 mL) was added (chloromethyl)benzene (15.01 mL, 130 mmol) at room temperature. The reaction mixture was heated at 75° C. overnight. Upon completion of reaction as indicated by LCMS and TLC the reaction mixture was filtered and the filtrate was concentrated. The residue was then dissolved in DCM (250 mL) and washed with aqueous sodium hydroxide solution (1 N, 2×100 mL) and brine (1×100 mL). The combined organic layers were dried over anhydrous magnesium sulfate, concentrated, and purified by silica gel chromatography (0%-80% ethyl acetate in hexanes) to yield (1S,3R)-3-(dibenzylamino)cyclohexanol (11.70 g, 91%) as a thick yellow oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.26-7.37 (m, 8H), 7.17-7.22 (m, 2H), 4.56 (d, J=4.30 Hz, 1H), 3.57 (s, 4H), 3.16-3.26 (m, 1H), 2.41 (tt, J=3.17, 11.86 Hz, 1H), 1.99-2.06 (m, 1H), 1.72 (d, J=8.20 Hz, 2H), 1.63-1.69 (m, 1H), 1.18-1.28 (m, 2H), 0.98 (t, 2H); MS (ESI) m/z 296.4 [M+1]+.

1. customUpon completion of reaction
2. filtrationwas filtered
3. concentrationthe filtrate was concentrated
4. dissolutionThe residue was then dissolved in DCM (250 mL)
5. washwashed with aqueous sodium hydroxide solution (1 N, 2×100 mL) and brine (1×100 mL)
6. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
7. concentrationconcentrated
8. custompurified by silica gel chromatography (0%-80% ethyl acetate in hexanes)

ORD record

ord-4f7f31fc26db4f1abf7a3b308901e536

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09139534B2