Tetrahydrofuran → 2-Cyclohexyl-5-(hydroxymethyl)benzonitrile

HRID 2040546Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:6](OC)=[O:7])#[N:2].[BH4-].[Li+].O1CCCC1>O1CCOCC1>[CH:13]1([C:12]2[CH:11]=[CH:10][C:5]([CH2:6][OH:7])=[CH:4][C:3]=2[C:1]#[N:2])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of methyl 3-cyano-4-cyclohexylbenzoate (299.0 mg, 1.229 mmol) in 1,4-dioxane (30 mL) was added 2 M lithium borohydride solution in tetrahydrofuran (1.23 mL, 2.46 mmol). The mixture was heated under reflux for 2.5 h. The mixture was cooled to 0° C. and quenched with 1 N aqueous HCl solution slowly to pH 5. After the addition of brine solution, the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure and purified by silica gel column chromatography to provide the title compound as a white solid (190.5 mg). LCMS m/z=216.5 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 1.23-1.33 (m, 1H), 1.41-1.52 (m, 4H), 1.76-1.83 (m, 1H), 1.84-1.92 (m, 4H), 2.90-3.05 (m, 1H), 4.70 (d, J=5.81 Hz, 2H), 7.36 (d, J=8.21 Hz, 1H), 7.53 (dd, J=8.27, 1.71 Hz, 1H), 7.61 (d, J=1.39 Hz, 1H).

Workup

temperatureThe mixture was heated
temperatureunder reflux for 2.5 h
customquenched with 1 N aqueous HCl solution slowly to pH 5
additionAfter the addition of brine solution
extractionthe mixture was extracted with ethyl acetate
dry with materialThe organic layer was dried over anhydrous sodium sulfate
concentrationconcentrated under reduced pressure
custompurified by silica gel column chromatography

Sources & evidence

ORD record: ord-36893ac97aaa497a8b251c0c0bd407c4
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580841B2

Reaction notes

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