METHYL 5-AMINOSALICYLATE

METHYL 5-AMINOSALICYLATE Property

Melting point:

95-99 °C (lit.)

Boiling point:

319.2±27.0 °C(Predicted)

Density 

1.305±0.06 g/cm3(Predicted)

storage temp. 

Keep in dark place,Sealed in dry,Room Temperature

solubility 

Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)

form 

Solid

pka

10.02±0.18(Predicted)

color 

Pale Yellow to Brown

CAS DataBase Reference

42753-75-3(CAS DataBase Reference)

Safety

Hazard Codes 

Xn

Risk Statements 

22-36/37/38-43

Safety Statements 

26

WGK Germany 

2

RTECS 

VO1683100

HazardClass 

IRRITANT

HS Code 

2922500090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H317May cause an allergic skin reaction

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

METHYL 5-AMINOSALICYLATE Chemical Properties,Usage,Production

Uses

5-Amino-2-hydroxybenzoic Acid Methyl Ester is disubsituted benzoic acid used in the preparation of various pharmaceutical compounds such as sphingosine kinase inhibitors.

Synthesis

In a 5-liter four-necked flask equipped with a reflux condenser, a dropping funnel, a thermometer casing, and a mechanical stirrer, methanol (3500 mL) and 5-aminosalicylic acid (500 g, 3.26 mol) were added and stirring was turned on. The reaction temperature was controlled in the range of 35-40 °C and thionyl chloride (600 mL, 8.16 mol) was added slowly dropwise for about 2 hours. After the dropwise addition, the reaction mixture was heated and refluxed for 15-16 hours, during which the reaction mixture gradually changed to a brown dilute slurry. The progress of the reaction was monitored by thin layer chromatography (TLC) until the residue of 5-aminosalicylic acid was below 1.0% (based on TLC analysis). Subsequently, the following post-treatment was carried out: first, about 2000 mL of methanol was removed by distillation at atmospheric pressure, and then the remaining methanol was azeotropically distilled (3 × 1000 mL) with water at reduced pressure (200-250 mmHg) to obtain a slurry. The slurry was poured into water (3500 mL) and the pH was adjusted first to 5.0 with 25% (w/v) NaOH solution (750 mL) and then to 7.0-7.5 with 20% (w/v) Na2CO3 solution (300 mL).The precipitated solid of methyl 5-amino salicylate was filtered and washed with water (2 x 1000 mL). The filter cake was dried to constant weight at 65 °C under reduced pressure (250 mmHg) to give 490 g of product in 90% yield. Melting point: 93-95°C. Reference: EP 0291159. 1H-NMR (CDCl3) data: δ 3.92 ppm (3H, s, Ar-COOCH3); 6.85 ppm (2H, m, Ar-H); 7.16 ppm (1H, d, J=2.73 Hz, Ar-H). Mass spectral data: m/z 167 (M+), 135, 107, 79.

References

[1] Journal of Organic Chemistry, 2011, vol. 76, # 15, p. 5873 - 5881
[2] Journal of Organic Chemistry, 2008, vol. 73, # 16, p. 6152 - 6157
[3] European Journal of Organic Chemistry, 2009, # 13, p. 2055 - 2058
[4] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 1, p. 189 - 192
[5] Patent: US2004/132982, 2004, A1. Location in patent: Page 4