Dimethyl Sulfate → Methyl 4-fluoro-3-nitrobenzoate

Participants

Reaction Conditions

Reaction Steps

Lithium hydroxide monohydrate (4.5 g, 1 eq) is added in small portions to a solution of 4-fluoro-3-nitrobenzoic acid (20 g, 1 eq) in tetrahydrofuran (100 ml). After stirring for 1 hour at approximately 20° C., dimethylsulphate (10.2 ml) is added dropwise to the yellow precipitate. The reaction mixture is then heated under reflux for 8 hours then concentrated under reduced pressure at 40° C. The residue is diluted in dichloromethane and Na2C0-3 saturated water. After decanting and extracting, the combined organic phases are washed with salt water, dried over sodium sulphate and concentrated under reduced pressure at 40° C. The yellow solid obtained is recrystallized from a diethyl ether/petroleum ether mixture in order to produce the expected compound in the form of a light yellow powder (16.7 g, 78% yield). Melting point=59° C.

Provenance & Evidence