Dimethyl Sulfate → Methyl 4-fluoro-3-nitrobenzoate

HRID 883687Notes

Reaction equation

HRID 883687 reaction equation
O.[OH-].[Li+].[F:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[CH:7][C:6]=1[N+:14]([O-:16])=[O:15].[CH3:17]OS(OC)(=O)=O>O1CCCC1>[F:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([O:11][CH3:17])=[O:10])=[CH:7][C:6]=1[N+:14]([O-:16])=[O:15]

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 679874-Fluoro-3-nitrobenzoic acidHCID 168937Lithium hydroxide, monohydrate

Product 1

HCID 5219721Methyl 4-fluoro-3-nitrobenzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

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 Na2CO3 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.

Workup

  1. temperatureThe reaction mixture is then heated
  2. temperatureunder reflux for 8 hours
  3. concentrationthen concentrated under reduced pressure at 40° C
  4. additionThe residue is diluted in dichloromethane
  5. customAfter decanting
  6. extractionextracting
  7. washthe combined organic phases are washed with salt water
  8. dry with materialdried over sodium sulphate
  9. concentrationconcentrated under reduced pressure at 40° C
  10. customThe yellow solid obtained
  11. customis recrystallized from a diethyl ether/petroleum ether mixture in order

Sources & evidence

ORD record
ord-837479cda10e4cf595c38850f4903f9b
Source dataset
uspto-grants-2012_08
Patent number
US08236965B2

Reaction notes

Loading…