Toluene → 2-Fluoro-1-methoxy-3-methyl-4-nitrobenzene

HRID 1962881Notes

Reaction equation

C[Zn]C.[C:4]1(C)C=CC=CC=1.Br[C:12]1[C:17]([F:18])=[C:16]([O:19][CH3:20])[CH:15]=[CH:14][C:13]=1[N+:21]([O-:23])=[O:22].[NH4+].[Cl-]>O1CCOCC1.CO>[F:18][C:17]1[C:12]([CH3:4])=[C:13]([N+:21]([O-:23])=[O:22])[CH:14]=[CH:15][C:16]=1[O:19][CH3:20]

Participants

Conditions

Temperature: 55 °C

Procedure

Dimethylzinc (67 ml of a 2M toluene) was slowly added to a mixture of 2-bromo-3-fluoro-4-methoxy-1-nitro-benzene (12.0 g) and palladium-(diphenylphosphinoferrocenyl)-dichloride-methylene dichloride complex (1.65 g) in dioxane (300 ml) at 40° C. The mixture was stirred at 55° C. during 2 hours. After cooling to room temperature, MeOH (80 ml) was slowly added followed by aqueous NH4Cl soln. The resulting mixture was extracted with ethyl acetate. The organic phase was washed with brine, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The crude oil was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate, 9/1) to provide 2-fluoro-1-methoxy-3-methyl-4-nitro-benzene (10.5 g, 90% purity) as a light yellow solid used as such in Step 3. 1H NMR (CDCl3) δ ppm: 7.89 (1H, dd); 6.86 (1H, dd); 3.96 (3H, s); 2.53 (3H, d).

Workup

temperatureAfter cooling to room temperature
extractionThe resulting mixture was extracted with ethyl acetate
washThe organic phase was washed with brine
dry with materialdried over anhydrous sodium sulphate
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe crude oil was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate, 9/1)

Sources & evidence

ORD record: ord-9143502f808e47a8b18f0114f8169415
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415272B2

Reaction notes

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