ETHYL 5-METHYLINDOLE-2-CARBOXYLATE

ETHYL 5-METHYLINDOLE-2-CARBOXYLATE Property

Melting point:

162-164°C

Boiling point:

236°C 4mm

Density 

1.177±0.06 g/cm3(Predicted)

Flash point:

236°C/4mm

storage temp. 

Sealed in dry,Room Temperature

pka

15.19±0.30(Predicted)

form 

crystalline powder

color 

Light yellow to beige

Water Solubility 

Soluble in methanol, and dichloromethane. Insoluble in water.

BRN 

159437

InChI

InChI=1S/C12H13NO2/c1-3-15-12(14)11-7-9-6-8(2)4-5-10(9)13-11/h4-7,13H,3H2,1-2H3

InChIKey

KMVFKXFOPNKHEM-UHFFFAOYSA-N

SMILES

N1C2=C(C=C(C)C=C2)C=C1C(OCC)=O

CAS DataBase Reference

16382-15-3(CAS DataBase Reference)

Safety

Safety Statements 

22-24/25

WGK Germany 

3

HS Code 

2933998090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

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

P305IF IN EYES:

P351Rinse cautiously with water for several minutes.

ETHYL 5-METHYLINDOLE-2-CARBOXYLATE Chemical Properties,Usage,Production

Uses

Reactant for synthesis of oxazino[4,3-a]indoles via cascade addition-cyclization reactions 1 Reactant for preparation of indolecarboxamides as cannabinoid CB1 receptor antagonists 2 Reactant for preparation of indole-3-propionic acids as antiinflammatory and analgesic agents 3 Reactant for Friedel-Crafts acylation with nitrobenzoyl chloride 4 Reactant for oximation reactions 5

Uses

Reactant for synthesis of oxazino[4,3-a]indoles via cascade addition-cyclization reactions, reactant for preparation of indolecarboxamides as cannabinoid CB1 receptor antagonists, reactant for preparation of indole-3-propionic acids as antiinflammatory and analgesic agents, reactant for Friedel-Crafts acylation with nitrobenzoyl chloride. Indole ring system is an important building block or intermediate in the synthesis of many pharmaceutical agents. It is formed during the Fischer indolization of ethyl pyruvate 2-[2-(methanesulfonyloxy)-4-methyl]phenylhydrazine. ? Reactant for oximation reactions

General Description

Ethyl 5-methylindole-2-carboxylate (5-Methylindole-2-carboxylic acid ethyl ester) is an indole derivative. Indole ring system is an important building block or intermediate in the synthesis of many pharmaceutical agents. It is formed during the Fischer indolization of ethyl pyruvate 2-[2-(methanesulfonyloxy)-4-methyl]phenylhydrazine.

Synthesis

1. 7.2 g (0.104 mol) of sodium nitrite dissolved in 40 ml of water was slowly added to a mixed solution containing 10.7 g (0.1 mol) of 4-methylaniline, 74 ml of 12N hydrochloric acid, and 140 ml of water at 5°C. 2. The reaction mixture was kept stirring at 5°C for 15 min, followed by the addition of 8.1 g of sodium acetate for neutralization. 3. 12.33 g (0.085 mol) of α-methylethyl acetoacetate and 80 ml of ethanol dissolved in 20 ml of water was added in another three-necked flask. three-necked flask, 12.33 g (0.085 mol) of α-methylethyl acetoacetate and 80 ml of ethanol were added, followed by the addition of 4.8 g (0.085 mol) of potassium hydroxide dissolved in 20 ml of water and 100 g of ice at 0° C. 4. The diazonium salt solution prepared in step 1 was added slowly and dropwise at 0° C. to the reaction mixture from step 3, and after completion of the dropwise addition, the mixed The system was left to react at 0°C for 18 h. 5. After completion of the reaction, the aqueous phase was extracted four times using 50 ml of ethyl acetate, and all the organic phases were combined and dried with anhydrous sodium sulfate. 6. The dried organic phase was concentrated, and the residue was dissolved in 100 ml of toluene, to which 16.3 g (0.085 mol) of p-toluenesulfonic acid monohydrate was added. 7. The reaction mixture was heated slowly to 110 °C and maintained at this temperature for 5 h. 8. At the end of the reaction, the reaction was cooled to room temperature, saturated sodium carbonate solution was added, the insoluble material was removed by filtration, and the organic phase was separated by static partitioning. 9. The organic phase was dried over anhydrous sodium sulfate and concentrated, and the residue was purified by column chromatography on silica gel in the eluent ratio of 30/70 (v/v) dichloromethane/cyclohexane to yield beige crystals with a melting point of 94 °C, with a yield of 25%.

References

[1] Patent: US2004/43995, 2004, A1. Location in patent: Page 13