Sodium Cyanide → 5-(1-(3-(Tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)pentanenitrile

HRID 1855050Notes

Reaction equation

CS(O[CH2:6][CH2:7][CH2:8][CH2:9][C:10]12[CH2:17][CH2:16][C:13]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH:25]4[CH2:30][CH2:29][CH2:28][CH2:27][O:26]4)[CH:19]=3)([CH2:14][CH2:15]1)[O:12][CH2:11]2)(=O)=O.[C-:31]#[N:32].[Na+]>CN(C=O)C.CCOC(C)=O>[O:26]1[CH2:27][CH2:28][CH2:29][CH2:30][CH:25]1[O:24][C:20]1[CH:19]=[C:18]([C:13]23[CH2:14][CH2:15][C:10]([CH2:9][CH2:8][CH2:7][CH2:6][C:31]#[N:32])([CH2:17][CH2:16]2)[CH2:11][O:12]3)[CH:23]=[CH:22][CH:21]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 4-(1-(3-(tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo [2.2.2]octan-4-yl)butyl methanesulfonate (133 mg, 0.303 mmol) and NaCN (60 mg, 1.224 mmol) in DMF (2 mL) was stirred at 60° C. for 18 h. The reaction was cooled to rt and diluted with EtOAc (6 mL). The organic phase was washed with water (5×5 mL), dried (MgSO4), and concentrated in vacuo to afford the title compound (102 mg, 91% yield) as a light yellow oil. LCMS, [M+H]+=370.5. 1H NMR (500 MHz, CDCl3) δ 7.23 (t, J=8.0 Hz, 1H), 7.13-7.10 (m, 1H), 7.01 (ddd, J=7.8, 1.6, 1.0 Hz, 1H), 6.94 (ddd, J=8.2, 2.5, 0.9 Hz, 1H), 5.45 (t, J=3.2 Hz, 1H), 3.98-3.89 (m, 1H), 3.83 (s, 2H), 3.66-3.57 (m, 1H), 2.38 (t, J=7.1 Hz, 2H), 2.10-1.96 (m, 5H), 1.90-1.81 (m, 2H), 1.75-1.55 (m, 10H), 1.49-1.37 (m, 2H), 1.22-1.14 (m, 2H).

Workup

temperatureThe reaction was cooled to rt
washThe organic phase was washed with water (5×5 mL)
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-c3a3294132ff40c2b0a9d7c50c8121ab
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08962660B2

Reaction notes

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