Methanol → 1-(Hydroxymethyl)cyclohexane-1-carbonitrile

To a solution of methyl 1-cyanocyclohexanecarboxylate (prepared according to Fleming et. al, J. Org. Chem. 2005, 70, 2200) (8.54 g, 51.10 mmol) in anhydrous tetrahydrofuran (300 mL) was added anhydrous methanol (3.1 mL, 78.00 mmol) and lithium borohydride (4.0 M solution in tetrahydrofuran 19 mL, 76 mmol). The reaction solution was heated to reflux under a nitrogen atmosphere for 4 hours, cooled to ambient temperature. The mixture was quenched by the slow addition of saturated aqueous ammonium chloride (5 mL). The mixture was diluted with ethyl acetate (400 mL), washed with a 2:1 mixture of saturated aqueous ammonium chloride and water (2×300 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford the title compound as a colorless oil (6.30 g, 89%): 1H NMR (300 MHz, CDCl3) δ 3.55 (s, 2H), 2.78 (br s, 1H), 1.98-1.93 (m, 2H), 1.74-1.69 (m, 4H), 1.63-1.48 (m, 4H).

1. temperatureThe reaction solution was heated
2. temperatureto reflux under a nitrogen atmosphere for 4 hours
3. customThe mixture was quenched by the slow addition of saturated aqueous ammonium chloride (5 mL)
4. additionThe mixture was diluted with ethyl acetate (400 mL)
5. washwashed with a 2:1 mixture of saturated aqueous ammonium chloride and water (2×300 mL)
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD record

ord-68d2af3a85f6434bb5603d83d0d4a4b6

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952169B2