Methanol → Methyl 3,5-difluoro-4-nitrobenzoate
Reaction equation
S(Cl)(Cl)=[O:2].[F:5][C:6]1[CH:7]=[C:8]([CH:11]=[C:12]([F:17])[C:13]=1[N+:14]([O-:16])=[O:15])[C:9]#N.[CH3:18][OH:19]>>[CH3:18][O:19][C:9](=[O:2])[C:8]1[CH:7]=[C:6]([F:5])[C:13]([N+:14]([O-:16])=[O:15])=[C:12]([F:17])[CH:11]=1Participants
Conditions
- Temperature
- 25 °C
Procedure
Thionylchloride (1.0 mol, 134 mL) was added to MeOH (400 mL) at −10° C. to −20° C. over a period of 0.5 h. To this solution was added 3,5-difluoro-4-nitro-benzonitrile (33.5 g, 180 mmol) and the reaction mixture was allowed to warm to 25° C. and stirred overnight at 25° C. Afterwards the temperature was slowly increased to 50° C. over 2 h and the evolving gas was trapped in a gas washer. Finally the reaction mixture was heated at reflux for 2 h. The cooled reaction mixture was filtered and concentrated. The crude product was dissolved in EtOAc and washed with cold aq. NaHCO3 solution and brine, dried over MsSO4, filtered and concentrated. The residue was crystallized from EtOAc-hexane to yield the title compound as an orange solid: TLC (hexane-EtOAc 3:1) Rf=0.38; HPLC RtA=1.74 min; 1H NMR (400 MHz, CDCl3): δ 7.76 (d, 2H), 3.98 (s, 3H).
Workup
- temperatureAfterwards the temperature was slowly increased to 50° C. over 2 h
- temperatureFinally the reaction mixture was heated
- temperatureat reflux for 2 h
- customThe cooled reaction mixture
- filtrationwas filtered
- concentrationconcentrated
- dissolutionThe crude product was dissolved in EtOAc
- washwashed with cold aq. NaHCO3 solution and brine
- customdried over MsSO4
- filtrationfiltered
- concentrationconcentrated
- customThe residue was crystallized from EtOAc-hexane
Sources & evidence
- ORD record
- ord-7fe8ac4ab9944597b8b3f7da20e6e22f
- Source dataset
- uspto-grants-2012_01
- Patent number
- US08093406B2
Reaction notes
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