Methanol → Ethyl 3-(4-methyl-1H-pyrrol-3-yl)propanoate

HRID 1937541Notes

Reaction equation

HRID 1937541 reaction equation
[C:1]([CH2:4][CH2:5][C:6]1[C:10]([CH3:11])=[CH:9][NH:8][CH:7]=1)([OH:3])=[O:2].CO.[CH3:14][C:15]1C=CC(S(N(N=O)C)(=O)=O)=CC=1.[OH-].[K+]>C(OCC)C.C(O)C.O>[CH2:14]([O:2][C:1]([CH2:4][CH2:5][C:6]1[C:10]([CH3:11])=[CH:9][NH:8][CH:7]=1)=[O:3])[CH3:15]

Participants

8

Reactant 4

HCID 887MethanolHCID 6628DiazaldHCID 14797Potassium HydroxideHCID 151607513-(4-Methyl-1H-pyrrol-3-yl)propanoic acid

Product 1

HCID 10877744Ethyl 3-(4-methyl-1H-pyrrol-3-yl)propanoateYield 80.6%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
70 °C

Procedure

3-(2-Carboxyethyl)-4-methylpyrrole (123 g) was mixed with 1500 mL of ethyl ether and 250 mL of methanol in a magnetically stirred receiver flask. A separate 3 L, 3 neck round bottom flask was equipped with magnetic stirring, a distillation head and condenser leading to the inlet of the receiver flask, and heated in a water bath. Into the 3 L flask was placed 240 g of Diazald dissolved in 1800 mL of ethyl ether and a solution of 73 g of potassium hydroxide dissolved in 360 mL of 95% ethanol and 112 mL of water. The 3 L flask was stirred and heated to 65-75° C. in a water bath and the diazomethane-ether mixture was distilled into the stirred receiver flask over about 2.5 hours. Ethyl ether (200 mL) was added to the 3 L flask and the distillation continued until complete. The receiver flask was stirred for another 30 minutes and then 10 mL of acetic acid was added. The mixture was extracted twice with 500 mL of water, then twice with 200 mL of saturated sodium bicarbonate. The ether layer was dried over anhydrous sodium sulfate and distilled to leave a dark fluid residue. The residue was distilled twice through a 4 inch Vigreux column and once through a 10 inch vacuum-jacketed Vigreux column to give 108 g (80.6% yield) of 3-(2-ethoxycarbonylethyl)-4-methylpyrrole. BP 108-113° C. at 0.5 mm.

Workup

  1. customA separate 3 L, 3 neck round bottom flask was equipped with magnetic stirring
  2. temperatureheated in a water bath
  3. distillationthe diazomethane-ether mixture was distilled into the stirred receiver flask over about 2.5 hours
  4. additionEthyl ether (200 mL) was added to the 3 L flask
  5. distillationthe distillation
  6. stirringThe receiver flask was stirred for another 30 minutes
  7. addition10 mL of acetic acid was added
  8. extractionThe mixture was extracted twice with 500 mL of water
  9. dry with materialThe ether layer was dried over anhydrous sodium sulfate
  10. distillationdistilled
  11. customto leave a dark fluid residue
  12. distillationThe residue was distilled twice through a 4 inch Vigreux column and once through a 10 inch vacuum-jacketed Vigreux column

Sources & evidence

ORD record
ord-f35c3d9c00ee4e74aa7e2d4473b4b6a6
Source dataset
uspto-grants-2002_05
Patent number
US06395734B1

Reaction notes

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