1-Methyl-3-nitrophthalate Chemical Properties

Melting point:

160.0 to 164.0 °C

Boiling point:

409.2±35.0 °C(Predicted)

Density 

1.484±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

solubility 

soluble in Acetone, Dichloromethane, Ethyl Acetate, Methanol

form 

Solid:particulate/powder

pka

1.87±0.30(Predicted)

color 

White to Almost white

CAS DataBase Reference

21606-04-2(CAS DataBase Reference)

Safety Information

HS Code 

2917.39.7000

1-Methyl-3-nitrophthalate Usage And Synthesis

Chemical Properties

light yellow crystalline powder

Uses

Methyl 3-Nitrophthalate is an intermediate in the synthesis of (αS)-3-Ethoxy-4-methoxy-α-[(methylsulfonyl)methyl]-N-[(1S)-1-phenylethyl]-benzenemethanamine which is an impurity of Apremilast (A729700), which is an oral phosphodiesterase 4 inhibitor used for treating psoriatic arthritis.

Synthesis

1. 3-Nitrophthalic acid (500 g, 2.37 moles) was slowly added to a pre-cooled mixture of 2500 ml of methanol and 260 ml of thionyl chloride in an ice bath. 2. The reaction mixture was heated to reflux and maintained for about 24 h. 3. Upon completion of the reaction, the reaction solution was concentrated under reduced pressure, followed by removal of excess thionyl chloride under nitrogen protection. 4. 1500 ml of toluene was added to the residue, mixed thoroughly and filtered. 5. The resulting solid product was dried at 60-70°C to give 522.0 g (98% yield) of 2-carboxy-phthalic acid. 6. 4. 1500 ml of toluene was added to the residue, mixed thoroughly and filtered. 5. The resulting solid product was dried at 60-70 °C to give 522.0 g (98% yield) of methyl 2-carboxy-3-nitrobenzoate, which was essentially free of 3-nitrodimethylphthalate. 6. A further 500 g of 3-nitrophthalic acid was taken and mixed with 2.5 liters of methanol in a round-bottomed flask. The mixture was cooled to 5-10°C. 7. 259.5 ml of thionyl chloride was added dropwise under constant stirring for 60-90 minutes. 8. After the dropwise addition, the reaction mixture was heated to 60-65°C and kept reacting for 20-25 hours. 9. After the reaction was completed, all solvents were removed by distillation at 60-65°C. 10. 1500 ml of toluene was added and stirred for 5-6 hours under nitrogen atmosphere. 11. stirred under nitrogen atmosphere for 5-6 h. 11. The solid product was isolated by filtration, washed with 500 ml of toluene and subsequently dried at 55-65 °C for 5-10 h. 525 g of 3-nitrophthalic acid-1-methyl ester (compound of formula II) was obtained in the final product.

References

[1] Patent: WO2006/15134, 2006, A1. Location in patent: Page/Page column 13
[2] Journal of Organic Chemistry, 1986, vol. 51, # 17, p. 3308 - 3314
[3] Monatshefte fuer Chemie, 1900, vol. 21, p. 791
[4] Chemische Berichte, 1901, vol. 34, p. 680
[5] Monatshefte fuer Chemie, 1900, vol. 21, p. 791

1-Methyl-3-nitrophthalate(21606-04-2)Related Product Information

• Bensulfuron methyl
• Kresoxim-methyl
• Methyl 2-iodobenzoate
• METSULFURON METHYL
• Methyl 2-(chlorosulfonyl)benzoate
• 3-Nitrobenzoic acid
• Methylparaben
• Methyl acetate
• Methyl benzoate
• 4-Nitrobenzoic acid
• 2-Nitrobenzoic acid
• Methyl acrylate
• 3-Nitrophthalic acid
• Thiophanate-methyl
• (R)-1-(3-Ethoxy-4-Methoxyphenyl)-2-(Methylsulfonyl)ethylaMine
• Apremilast Impurity 34
• (S)-1-(3-Ethoxy-4-Methoxyphenyl)-2-(Methylsulfonyl)ethylaMine N-acetyl-L-leucine salt
• Apremilast Impurity 28