Sodium Cyanide → HCID 90408448, compound

HRID 1855088Notes

Reaction equation

HRID 1855088 reaction equation
CS(O[CH2:6][CH2:7][C:8]12[CH2:15][CH2:14][C:11]([C:16]3[CH:21]=[C:20]([O:22][CH:23]4[CH2:28][CH2:27][CH2:26][CH2:25][O:24]4)[CH:19]=[C:18]([F:29])[CH:17]=3)([CH2:12][CH2:13]1)[O:10][CH2:9]2)(=O)=O.[C-:30]#[N:31].[Na+]>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].CS(C)=O.CCOC(C)=O>[F:29][C:18]1[CH:17]=[C:16]([C:11]23[CH2:14][CH2:15][C:8]([CH2:7][CH2:6][C:30]#[N:31])([CH2:13][CH2:12]2)[CH2:9][O:10]3)[CH:21]=[C:20]([O:22][CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)[CH:19]=1

Participants

6

Reactant 2

HCID 8929Sodium CyanideHCID 90408426HCID 90408426, compound

Product 1

HCID 90408448HCID 90408448, compoundYield 92.2%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 2-(1-(3-fluoro-5-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)ethyl methanesulfonate (0.45 g, 1.05 mmol), NaCN (0.309 g, 6.30 mmol), and Bu4NI (0.039 g, 0.105 mmol) in DMSO (10 mL) was stirred at 85° C. for 18 h, then was cooled to rt and diluted with EtOAc (10 mL). The organic phase was washed with water (3×), dried (MgSO4), filtered, and concentrated in vacuo. The residual crude oil was chromatographed (SiO2; gradient from 0% to 30% EtOAc/hexane over 10 min) to give the title compound (0.348 g, 0.968 mmol, 92% yield) as a clear oil. 1H NMR (CDCl3) δ: 6.86 (t, J=1.8 Hz, 1H), 6.74 (dt, J=10.1, 1.9 Hz, 1H), 6.69 (dt, J=10.6, 2.3 Hz, 1H), 5.40 (t, J=3.2 Hz, 1H), 3.93-3.86 (m, 1H), 3.85-3.81 (m, 2H), 3.62 (dtd, J=11.4, 4.1, 1.4 Hz, 1H), 2.32 (dd, J=8.6, 7.3 Hz, 2H), 2.07-1.96 (m, 4H), 1.88-1.80 (m, 2H), 1.79-1.55 (m, 10H); 19F NMR (CDCl3) δ: −111.9.

Workup

  1. temperaturewas cooled to rt
  2. washThe organic phase was washed with water (3×)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residual crude oil was chromatographed (SiO2; gradient from 0% to 30% EtOAc/hexane over 10 min)

Sources & evidence

ORD record
ord-4063a26ec3094346a98d43551fbee884
Source dataset
uspto-grants-2015_02
Patent number
US08962660B2

Reaction notes

Loading…