Chloral → 5-cyano-1-methyl-1H-pyrrole-2-acetic acid

An ether (10 ml) solution of N-methylpyrrole (810 mg, 10 mmol) and chloral (1.6 g, 10.7 mmol) was refluxed for 24 hours. The solvent was removed at room temperature under vacuum and the residue was dissolved in methanol (30 ml). This solution was added to a solution of sodium cyanide (3.0 g, 60 mmol) in water (30 ml). To this solution, heated to 30°-35° C. in an oil bath, was added during 20 hours a solution of potassium hydroxide (2.6 g, 40 mmol) in water (15 ml). After completion of the addition, the mixture was kept at the same temperature for 2 additional hours. The mixture was then diluted with water and washed with methylene chloride (this organic layer contains almost no starting material). The aqueous layer was acidified carefully using hydrochloric acid and extracted with methylene chloride several times. The extracts were combined and washed with brine. After drying over magnesium sulfate, the organic solution was concentrated. The residue was chromatographed on silica-gel(hexane-ethyl acetate eluent) to give the desired cyano acid, 5-cyano-1-methylpyrrole-2-acetic acid (945 mg), the yield being 58%.

1. customThe solvent was removed at room temperature under vacuum
2. dissolutionthe residue was dissolved in methanol (30 ml)
3. temperatureTo this solution, heated to 30°-35° C. in an oil bath
4. additionAfter completion of the addition
5. washwashed with methylene chloride (this organic layer
6. extractionextracted with methylene chloride several times
7. washwashed with brine
8. dry with materialAfter drying over magnesium sulfate
9. concentrationthe organic solution was concentrated
10. customThe residue was chromatographed on silica-gel(hexane-ethyl acetate eluent)

ORD record

ord-1b6314b61a01450aacb6141154d3c83b

Source dataset

uspto-grants-1980_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04238396