Ethyl 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylate

Ethyl 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylate Property

Melting point:

164.0 to 168.0 °C

Boiling point:

358.4±42.0 °C(Predicted)

Density 

1.173±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

solubility 

DMSO (Slightly), Methanol (Slightly)

pka

14.65±0.50(Predicted)

form 

Solid

color 

Beige

λmax

297nm(EtOH)(lit.)

InChI

InChI=1S/C10H13NO3/c1-4-14-10(13)9-6(2)8(5-12)11-7(9)3/h5,11H,4H2,1-3H3

InChIKey

GDISALBEIGGPER-UHFFFAOYSA-N

SMILES

N1C(C=O)=C(C)C(C(OCC)=O)=C1C

CAS DataBase Reference

2199-59-9(CAS DataBase Reference)

NIST Chemistry Reference

5-Formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid ethyl ester(2199-59-9)

Safety

Hazard Codes 

Xi

Hazard Note 

Irritant

HS Code 

2933998090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

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.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

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.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

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

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

Ethyl 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylate Chemical Properties,Usage,Production

Chemical Properties

Brown crystals

Uses

5-ForMyl-2,4-diMethyl-1H-pyrrole-3-carboxylic Acid Ethyl Ester is used as an intermediate in the synthesis of receptor tyrosine kinase (RTK) inhibitors and their metabolites.

Synthesis

The general procedure for the synthesis of ethyl 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylate from ethyl 2,4-dimethylpyrrole-3-carboxylate was as follows: dimethylformamide (322 g) was mixed with dichloromethane (3700 mL) and cooled to 4 °C in an ice bath, followed by the slow addition of phosphorus trichloride (684 g) under stirring. Solid ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (670 g) was added in batches over 15 min and the maximum temperature was controlled at 18 °C during the reaction. The reaction mixture was heated to a reflux state maintained for 1 h. Subsequently, the temperature was raised to 15 °C by cooling to 10 °C and rapid addition of 1.6 L of ice water. 10N hydrochloric acid (1.6L) was added with vigorous stirring and the temperature was raised to 22°C. The reaction was allowed to stand for 30 minutes to allow the two phases to separate. The two phases were allowed to separate by standing for 30 minutes, during which time the maximum temperature reached 40°C. The pH of the aqueous phase was adjusted to 12-13 with 10N potassium hydroxide (3.8L), and the temperature was maintained at 55°C during the adjustment. After adjustment, the mixture was cooled to 10°C and stirred for 1 hour. The product was collected by vacuum filtration and washed four times with water to afford ethyl 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylate (778 g, 100% yield) as a yellow solid. The product was analyzed by 1H-NMR (DMSO-d6) and mass spectrometry to confirm the structure: 1H-NMR δ 1.25 (t, 3H, CH3), 2.44,2.48 (2*s, 2*3H, 2*CH3), 4.16 (q, 2H, CH2), 9.59 (s, 1H, CHO), 12.15 (br s, 1H, NH); MS m/z 195 [M+1].

References

[1] Patent: US2003/216410, 2003, A1
[2] Patent: US2003/130280, 2003, A1
[3] Patent: US2003/100555, 2003, A1
[4] Patent: US2002/32204, 2002, A1
[5] Patent: US2002/156292, 2002, A1