Sodium hydride → 1-Methoxy-3-methyl-2-nitro-4-(trifluoromethyl)benzene

HRID 1042669

Reaction equation

HRID 1042669 reaction equation
[H-].[Na+].[I-].[CH3:4][S+](C)C.[CH3:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=1[N+:20]([O-:22])=[O:21]>CS(C)=O.C1COCC1>[CH3:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[C:12]([CH3:4])[C:11]=1[N+:20]([O-:22])=[O:21]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 75127Trimethylsulfonium iodideHCID 967482-Nitro-4-trifluoromethylanisole

Product 1

HCID 594278831-Methoxy-3-methyl-2-nitro-4-(trifluoromethyl)benzene

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
15 °C

Procedure

1-methoxy-3-methyl-2-nitro-4-(trifluoromethyl)benzene was prepared by a procedure similar to that described in “Synthesis of 3,6-Disubstituted 2-Nitrotoluenes by Methylation of Aromatic Nitro Compounds with Dimethylsulfonium Methylide”, Kitano, Masafumi, Ohashi Naohito, Synthetic Communications, 30(23), 4247-4254, 2000. To a suspension of NaH (60% by wt. in mineral oil, 362 mg, 9.04 mmol) and trimethylsulfonium iodide (1.84 g, 9.04 mmol) in DMSO (17 ml) and THF (6.7 ml) was added 4-methoxy-3-nitrobenzotrifluoride (1.00 g, 4.52 mmol) as a solution in DMSO (2.7 ml). The reaction mixture was allowed to stir at 10-20° C. for 5 hrs. The reaction mixture was quenched by addition to ice water. The aqueous layer was separated and extracted with toluene 7 times. The combined organic extracts were washed with brine, dried over MgSO4, and filtered. The solvent was removed by distillation at reduced pressure. The residue was purified by automated silica gel chromatography (100% hexanes to 98:2 hexanes:ethylacetate) to provide 1-methoxy-3-methyl-2-nitro-4-(trifluoromethyl)benzene.

Workup

  1. custom1-methoxy-3-methyl-2-nitro-4-(trifluoromethyl)benzene was prepared by a procedure similar to
  2. customThe reaction mixture was quenched by addition to ice water
  3. customThe aqueous layer was separated
  4. extractionextracted with toluene 7 times
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customThe solvent was removed by distillation at reduced pressure
  9. customThe residue was purified by automated silica gel chromatography (100% hexanes to 98:2 hexanes:ethylacetate)

Sources & evidence

ORD record
ord-4e4ecf6b13fa4892ae486ed503e3bec3
Source dataset
uspto-grants-2013_10
Patent number
US08557996B2

Linked notes

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