Sodium hydride → 5-(Cyclopropylmethoxy)cyclohex-1-enecarbonitrile

HRID 1852485Notes

Reaction equation

[OH:1][CH:2]1[CH2:7][C:6]([C:8]#[N:9])=[CH:5][CH2:4][CH2:3]1.[H-].[Na+].Br[CH2:13][CH:14]1[CH2:16][CH2:15]1>CN(C)C=O.CCOC(C)=O>[CH:14]1([CH2:13][O:1][CH:2]2[CH2:7][C:6]([C:8]#[N:9])=[CH:5][CH2:4][CH2:3]2)[CH2:16][CH2:15]1

Participants

Conditions

Temperature: 75 °C

Procedure

To the solution of (R or S)-5-Hydroxycyclohex-1-enecarbonitrile (Intermediate #40, 2.0 g, 16 mmol) in N,N-dimethylformamide (10 mL) was added sodium hydride (850 mg, 21 mmol, 60% dispersion in oil) at 0° C. The resulting suspension was stirred at ambient temperature for 30 minutes before the addition of bromomethylcyclopropane (3.3 g, 24 mmol). The mixture was then stirred at 75° C. for 6 hours, and diluted with EtOAc (50 mL). The organic solution was washed with brine (2×10 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by MPLC on Silica gel (eluting with 2-5% EtOAc/hexane) to afford the title compound as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 6.63-6.62 (m, 1H), 3.69-3.66 (m, 1H), 3.34-3.32 (m, 2H), 2.54-2.49 (m, 1H), 2.38-2.30 (m, 1H), 2.29-2.24 (m, 2H), 1.85-1.83 (m, 1H), 1.75-1.72 (m, 1H), 1.08-1.04 (m, 1H), 0.59-0.54 (m, 2H), 0.24-0.20 (1,2H).

Workup

washThe organic solution was washed with brine (2×10 mL)
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude residue was purified by MPLC on Silica gel (eluting with 2-5% EtOAc/hexane)

Sources & evidence

ORD record: ord-07a325c52aaf42c3b6850d2f7803de99
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08962608B2

Reaction notes

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