Sodium hydride → 2-Methoxy-4-(oxiran-2-yl)benzonitrile

HRID 2175869Notes

Reaction equation

HRID 2175869 reaction equation
[H-].[Na+].[I-].[CH3:4][S+](C)C.[CH:8]([C:10]1[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[C:12]([O:18][CH3:19])[CH:11]=1)=[O:9]>C1COCC1.CS(C)=O>[CH3:19][O:18][C:12]1[CH:11]=[C:10]([CH:8]2[CH2:4][O:9]2)[CH:17]=[CH:16][C:13]=1[C:14]#[N:15]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 75127Trimethylsulfonium iodideHCID 600485344-Formyl-2-methoxybenzonitrile

Product 1

HCID 552967592-Methoxy-4-(oxiran-2-yl)benzonitrile

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a cool solution of NaH (0.16 g, 3.9 mmol) in THF (40 mL) was added dropwise a solution of trimethylsulfonium iodide (0.91 g, 4.5 mmol) in DMSO (20 mL). The resulting mixture was stirred at 0° C. under N2 for 20 min. A solution of 4-formyl-2-methoxybenzonitrile (0.60 g, 3.72 mmol) in THF (20 mL) was added. The resulting reaction mixture was stirred at 0° C. under N2 for 1 hr, and then it was warmed gradually to room temperature and stirred at that temperature for 12 hr. The starting material was consumed as indicated by TLC (25% ethyl acetate/hexanes). The reaction mixture was cooled to 0° C. and quenched with dropwise addition of water. The mixture was extracted with ethyl acetate (2×70 mL). The combined organic layers were washed with water, brine, then dried (MgSO4) and filtered. The filtrate was concentrated in vacuo. The residue was purified via column chromatography (silica gel, 10-30% EtOAc-hexanes) to afford 2-methoxy-4-(oxiran-2-yl)benzonitrile: 1H NMR (CDCl3, 500 MHz) δ 7.57 (d, J=8 Hz, 1H), 6.99 (dd, J=1.1 Hz, J=1.2 Hz, 1H), 6.89 (s, 1H), 3.97 (s, 3H), 3.94-3.92 (m, 1H), 3.22 (dd, J=5.2, Hz, J=4.1 Hz, 1H), 2.77 (d, J=2.5 Hz, 1H); LC/MS: (IE, m/z) [M+1]+=176.33.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at 0° C. under N2 for 1 hr
  3. temperatureit was warmed gradually to room temperature
  4. stirringstirred at that temperature for 12 hr
  5. customThe starting material was consumed
  6. temperatureThe reaction mixture was cooled to 0° C.
  7. customquenched with dropwise addition of water
  8. extractionThe mixture was extracted with ethyl acetate (2×70 mL)
  9. washThe combined organic layers were washed with water, brine
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationThe filtrate was concentrated in vacuo
  13. customThe residue was purified via column chromatography (silica gel, 10-30% EtOAc-hexanes)

Sources & evidence

ORD record
ord-6b2702deec1e491e858f4ada644c606d
Source dataset
uspto-grants-2015_06
Patent number
US09062070B2

Reaction notes

Loading…