Sodium Cyanide → 2-(1-(3-(tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)acetonitrile

HRID 1855041Notes

Reaction equation

I[CH2:2][C:3]12[CH2:10][CH2:9][C:6]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH:18]4[CH2:23][CH2:22][CH2:21][CH2:20][O:19]4)[CH:12]=3)([CH2:7][CH2:8]1)[O:5][CH2:4]2.[C-:24]#[N:25].[Na+]>CN(C=O)C.CCOC(C)=O>[O:19]1[CH2:20][CH2:21][CH2:22][CH2:23][CH:18]1[O:17][C:13]1[CH:12]=[C:11]([C:6]23[CH2:9][CH2:10][C:3]([CH2:2][C:24]#[N:25])([CH2:8][CH2:7]2)[CH2:4][O:5]3)[CH:16]=[CH:15][CH:14]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 4-(iodomethyl)-1-(3-(tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2]octane (1.5 g, 3.50 mmol) and NaCN (0.687 g, 14.01 mmol) in DMF (8 mL) was stirred at 80° C. for 18 h. The reaction was diluted with EtOAc (10 mL), washed with water (3×10 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo to give 2-(1-(3-(tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)acetonitrile (1.15 g, 3.50 mmol, 100% yield) as light brown oil. The above nitrile (1.15 g, 3.50 mmol) was taken up in ethylene glycol (20 mL) and treated with 40% KOH (5.00 mL, 35.0 mmol). The reaction was stirred at 165° C. for 18 h and concentrated in vacuo. The residue was dissolved in water (15 mL), acidified to pH 2 with 1 N aqueous HCl, and extracted with EtOAc (5×5 mL). The combined extracts were washed with brine, dried with MgSO4, filtered, and concentrated in vacuo to afford the title compound (0.91 g, 99% yield) as a light brown solid. LCMS, [M−H]+=261.3.

Workup

washwashed with water (3×10 mL)
dry with materialThe organic layer was dried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-8ae6b2f0a6f548eca041456d84f10bab
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08962660B2

Reaction notes

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