Methyl 5-fluoro-2-methyl-3-nitrobenzoate Chemical Properties

Boiling point:

297.7±40.0 °C(Predicted)

Density 

1.335±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

solubility 

Slightly soluble in water. Soluble in dimethyl sulfoxide and acetone.

color 

White

InChI

InChI=1S/C9H8FNO4/c1-5-7(9(12)15-2)3-6(10)4-8(5)11(13)14/h3-4H,1-2H3

InChIKey

QOEAMLSLLJPIRF-UHFFFAOYSA-N

SMILES

C(OC)(=O)C1=CC(F)=CC([N+]([O-])=O)=C1C

Safety Information

HS Code 

2916399090

Methyl 5-fluoro-2-methyl-3-nitrobenzoate Usage And Synthesis

Uses

Methyl 5-fluoro-2-methyl-3-nitrobenzoate is used in organic synthesis and it is used in the synthesis of 6-Fluoro-4-nitroisobenzofuran-1 (3H)-one.

Preparation

Methyl 5-fluoro-2-methyl-3-nitrobenzoate synthesis: To a solution of conc. H2SO4 (700mL) was added portionwise 5-fluoro-2-methylbenzoic acid (80g, 520 mmol) at -5-0°C. Then a mixture of conc. HNO3(60.4 g. 624 mmol) in conc. H2SO4 (60 mL) was added drop-wise at -5-0°C. in a period of about 1.5 hrs. After the addition, the mixture was stirred at this temperature for 2 hrs. TLC (petroleum ether/ EtOAc=1:1) showed the reaction was complete. The mixture was poured into crash ice with vigorous stirring and the precipitate was collected by filtration. The precipitate was dissolved in EtOAc, washed with brine, dried over anhydrous Na2SO4 concentrated to give crude 5-fluoro-2-methyl-3-nitrobenzoic acid (54 g). A solution of this crude 5-fluoro-2-methyl-3-nitrobenzoic acid (54 g) in dry methanol (500 mL) was cooled to 0°C., SOCl2 (64.52g, 542.3 mmol) was added drop-wise. After the addition, the mixture was heated to reflux for 16hrs. TLC (petroleum ether/EtOAc=1:1) showed the reaction was complete. Solvent was removed under reduced pressure to give crude product. The crude product was purified by silica gel chromatography (petroleum ether to petro leum ether/EtOAc=50: 1) to give methyl 5-fluoro-2-methyl-3-nitrobenzoate (28 g, yield 25% for two steps) as a white solid.

Synthesis

General method: 5-fluoro-2-methyl-3-nitrobenzoic acid (552 mmol) was dissolved in methanol and cooled to below 0°C. The solution was then dissolved in methanol. At this temperature, sulfoxide chloride (1100 mmol) was slowly added dropwise. After the dropwise addition, the reaction mixture was continued to be stirred. Subsequently, the reaction mixture was heated to reflux and maintained for 4 to 5 hours. Upon completion of the reaction, the mixture was slowly poured into 900 mL of ice water with stirring. The precipitated solid product was collected by filtration and dried to give the final methyl 2-methyl-3-nitro-5-fluorobenzoate.

References

[1] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 20, p. 4557 - 4561
[2] Patent: EP2098513, 2009, A1. Location in patent: Page/Page column 61-62
[3] Patent: WO2005/28445, 2005, A2. Location in patent: Page/Page column 29-30
[4] Patent: US2010/35883, 2010, A1. Location in patent: Page/Page column 65
[5] Organic Process Research and Development, 2012, vol. 16, # 12, p. 1897 - 1904

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