Dimethylformamide → 4-CYANO-1H-PYRROLE-2-CARBOXYLIC ACID METHYL ESTER

HRID 730533Notes

Reaction equation

HRID 730533 reaction equation
[CH3:1][O:2][C:3]([C:5]1[NH:6][CH:7]=[CH:8][CH:9]=1)=[O:4].ClS([N:14]=[C:15]=O)(=O)=O.CN(C)C=O>C(#N)C>[CH3:1][O:2][C:3]([C:5]1[NH:6][CH:7]=[C:8]([C:15]#[N:14])[CH:9]=1)=[O:4]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 70918Chlorosulfonyl isocyanateHCID 136930Methyl pyrrole-2-carboxylate

Product 1

HCID 109864094-CYANO-1H-PYRROLE-2-CARBOXYLIC ACID METHYL ESTERYield 45.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
-20 °C

Procedure

4-Cyano-1H-pyrrole-2-carboxylic acid methyl ester was prepared as described in Can. J. Chem., 59, 2673-76 (1981). 1H-Pyrrole-2-carboxylic acid methyl ester (2.00 g, 16.00 mmol) was dissolved in acetonitrile (5 mL) and the solution was cooled to −20° C. Chlorosulfonylisocyanate (3.40 g, 24.00 mmol) was dissolved in acetonitrile (5 mL) and added dropwise via syringe over a period of 5 min to the above solution. The solution was allowed to warm to 25° C. and was stirred for 20 h. The solution was cooled back to 0° C., N,N-dimethylformamide (2 mL) was added and the solution was heated to 50° C. for 15 min. The reaction mixture was poured into ice and was extracted with chloroform, washed with saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm, 40% ethyl acetate in hexanes) afforded the desired product, 4-cyano-1H-pyrrole-2-carboxylic acid methyl ester (1.09 g, 7.265 mmol, 45.4% yield) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ: 3.91 (3H, s), 7.12 (1H, t, J=2.0 Hz), 7.40-7.41 (1H, m), 9.60 (1H, bs). FT-IR (ATR) νmax (neat): 2228, 1691 cm−1.

Workup

  1. custom4-Cyano-1H-pyrrole-2-carboxylic acid methyl ester was prepared
  2. additionadded dropwise via syringe over a period of 5 min to the above solution
  3. temperatureto warm to 25° C.
  4. temperatureThe solution was cooled back to 0° C.
  5. temperaturethe solution was heated to 50° C. for 15 min
  6. additionThe reaction mixture was poured into ice
  7. extractionwas extracted with chloroform
  8. washwashed with saturated aqueous sodium bicarbonate solution
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customPurification by flash column chromatography (Merck silica gel 60, 40-63 μm, 40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-556fd6b4286046348ee4eca57a3bd6cb
Source dataset
uspto-grants-2009_09
Patent number
US07582754B2

Reaction notes

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