Sodium hydride → 2-Methoxy-5-methyl-4-(oxiran-2-yl)benzonitrile

HRID 1187008Notes

Reaction equation

HRID 1187008 reaction equation
[H-].[Na+].[I-].[CH3:4][S+](C)C.[CH:8]([C:10]1[C:17]([CH3:18])=[CH:16][C:13]([C:14]#[N:15])=[C:12]([O:19][CH3:20])[CH:11]=1)=[O:9]>C1COCC1.CS(C)=O>[CH3:20][O:19][C:12]1[CH:11]=[C:10]([CH:8]2[CH2:4][O:9]2)[C:17]([CH3:18])=[CH:16][C:13]=1[C:14]#[N:15]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 75127Trimethylsulfonium iodideHCID 772312524-Formyl-2-methoxy-5-methylbenzonitrile

Product 1

HCID 772312532-Methoxy-5-methyl-4-(oxiran-2-yl)benzonitrile

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a cool solution of NaH (1.20 g, 30.0 mmol) in THF (300 ml) was added dropwise a solution of trimethylsulfonium iodide (8.74 g, 42.8 mmol) in DMSO (80 mL). The resulting mixture was stirred at 0° C. under N2 for 20 min. The solution of 4-formyl-2-methoxy-5-methylbenzonitrile (5.00 g, 28.5 mmol) in THF (60 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 (2×200 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-5-methyl-4-(oxiran-2-yl)benzonitrile. 1H NMR (CDCl3, 500 MHz) δ 7.35 (s, 1H), 6.88 (s, 1H), 4.01 (s, 1H), 3.92 (s, 3H), 3.25 (s, 1H), 2.65 (d, J=2.6 Hz, 1H), 2.37 (s, 3H); LC/MS: (IE, m/z) [M+1]+=190.0; tR=2.85 min.

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 (2×200 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-e99d245aded543c3b93b5ec7df9d2acb
Source dataset
uspto-grants-2014_03
Patent number
US08673920B2

Reaction notes

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