2-O-tert-butyl 4-O-ethyl 5-formyl-3-methyl-1H-pyrrole-2,4-dicarboxylate → 2-O-tert-butyl 4-O-ethyl 5-[cyclopropyl(hydroxy)methyl]-3-methyl-1H-pyrrole-2,4-dicarboxylate

HRID 2191495Notes

Reaction equation

HRID 2191495 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[CH2:6]([O:8][C:9]([C:11]1[C:12]([CH3:25])=[C:13]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[NH:14][C:15]=1[CH:16]=[O:17])=[O:10])[CH3:7]>O1CCCC1>[CH2:6]([O:8][C:9]([C:11]1[C:12]([CH3:25])=[C:13]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[NH:14][C:15]=1[CH:16]([CH:1]1[CH2:3][CH2:2]1)[OH:17])=[O:10])[CH3:7]

Participants

4

Reactant 2

HCID 98142842-O-tert-butyl 4-O-ethyl 5-formyl-3-methyl-1H-pyrrole-2,4-dicarboxylateHCID 178418630HCID 178418630, compound

Product 1

HCID 498403972-O-tert-butyl 4-O-ethyl 5-[cyclopropyl(hydroxy)methyl]-3-methyl-1H-pyrrole-2,4-dicarboxylateYield 39.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

Cyclopropylmagnesium bromide (15 m, 0.5 mol/L) was cooled down to −10° C. in an ice-salt bath under an argon atmosphere. 5-Formyl-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 1b (1.26 g, 4.5 mmol) was dissolved in 10 ml of tetrahydrofuran under stirring, the resulting solution was added dropwise to the above solution while maintaining the temperature at −10° C. Upon completion of the addition, the ice-salt bath was removed, and the reaction mixture was stirred for 1 hour at room temperature. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was quenched with water, added with sulfuric acid solution (20 ml, 10%) and stirred for 30 minutes, and extracted with ethyl acetate (50 ml×3). The combined organic extracts were washed with saturated brine (50 ml), dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound 5-(cyclopropyl-hydroxy-methyl)-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 60a (576 mg, yield 39.6%) as a white solid.

Workup

  1. additionthe resulting solution was added dropwise to the above solution
  2. additionUpon completion of the addition
  3. customthe ice-salt bath was removed
  4. stirringthe reaction mixture was stirred for 1 hour at room temperature
  5. customthe reaction mixture was quenched with water
  6. additionadded with sulfuric acid solution (20 ml, 10%)
  7. stirringstirred for 30 minutes
  8. extractionextracted with ethyl acetate (50 ml×3)
  9. washThe combined organic extracts were washed with saturated brine (50 ml)
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. customto remove the drying agent
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3791bbc883e74b09bc531fa6e2d5cc59
Source dataset
uspto-grants-2012_12
Patent number
US08329682B2

Reaction notes

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