Methyl iodide → Methyl 3-bromo-2-fluoro-6-methyl-5-nitrobenzoate

HRID 1530293Notes

Reaction equation

HRID 1530293 reaction equation
[Br:1][C:2]1[C:3]([F:15])=[C:4]([C:8]([CH3:14])=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=1)[C:5]([OH:7])=[O:6].[C:16]([O-])([O-])=O.[K+].[K+].IC>CN(C)C=O.O>[Br:1][C:2]1[C:3]([F:15])=[C:4]([C:8]([CH3:14])=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=1)[C:5]([O:7][CH3:16])=[O:6]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 866726603-Bromo-2-fluoro-6-methyl-5-nitrobenzoic acid

Product 1

HCID 86672661Methyl 3-bromo-2-fluoro-6-methyl-5-nitrobenzoateYield 96%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-bromo-2-fluoro-6-methyl-5-nitrobenzoic acid (2.41 g, 8.67 mmol) in N,N-Dimethylformamide (25 ml) at room temperature and under nitrogen was added K2CO3 (2.4 g, 17.34 mmol) followed by iodomethane (0.7 ml, 11.27 mmol). The reaction mixture was stirred at room temperature for 2 hours before being diluted with deionized water (100 ml) and extracted with EtOAc (3×50 ml). The combined organic phases were washed with saturated NaHCO3 (aq) (50 ml) and then dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified twice by FCC (50 g silica, Isolute cartridge, gradient of eluents; 98:2 Heptane:EtOAc to 9:1 Heptane:EtOAc) to give 2.43 g (89%) of methyl 3-bromo-2-fluoro-6-methyl-5-nitrobenzoate as a white solid. LC-MS 99%, 2.18 min (3 minute LC-MS method), m/z=no ionization, 1H NMR (500 MHz, Chloroform-d) δ ppm 8.22 (d, J=6.2 Hz, 1H), 4.00 (s, 3H), 2.48 (s, 3H).

Workup

  1. extractionextracted with EtOAc (3×50 ml)
  2. washThe combined organic phases were washed with saturated NaHCO3 (aq) (50 ml)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified twice by FCC (50 g silica, Isolute cartridge, gradient of eluents; 98:2 Heptane:EtOAc to 9:1 Heptane:EtOAc)

Sources & evidence

ORD record
ord-b8c25b084a3748c796562fdec0688ca2
Source dataset
uspto-grants-2015_07
Patent number
US09090562B2

Reaction notes

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