tert-Butyl 2-formyl-1H-pyrrole-1-carboxylate → 2-(1-Hydroxy-prop-2-ynyl)-pyrrole-1-carboxylic acid tert-butyl ester

HRID 1860983Notes

Reaction equation

HRID 1860983 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:12]=[CH:11][CH:10]=[C:9]1[CH:13]=[O:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:15]([Mg]Cl)[CH3:16]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH:12]=[CH:11][CH:10]=[C:9]1[CH:13]([OH:14])[C:15]#[CH:16])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 5057005tert-Butyl 2-formyl-1H-pyrrole-1-carboxylateHCID 178461633HCID 178461633, compound

Product 1

HCID 112530122-(1-Hydroxy-prop-2-ynyl)-pyrrole-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-formyl-pyrrole-1-carboxylic acid tert-butyl ester (23.4 g, 120 mmol) (prepared as described below) in dry THF (275 mL) was added ethylmagnesium chloride (Aldrich, 0.5 M solution in THF, 480 mL, 240 mmol) dropwise at −65° C. and the reaction mixture was stirred at the same temperature for 0.5 hour. The cooling bath was then removed and the reaction mixture was stirred for another 1 hour to give a clear solution. The reaction was quenched by slowly adding EtOH (60 mL) and a saturated aqueous solution of NH4Cl (200 mL) at 5° C., and extracted with ethyl acetate (3×250 mL). The combined organic extracts were successively washed with water (200 mL) and brine (200 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Biotage, 75-S, 92/8 hexanes/ethyl acetate) purification of the crude oil afforded 2-(1-hydroxy-prop-2-ynyl)-pyrrole-1-carboxylic acid tert-butyl ester as a light amber oil. (Yield 25.0 g, 94.2%).

Workup

  1. customThe cooling bath was then removed
  2. stirringthe reaction mixture was stirred for another 1 hour
  3. customto give a clear solution
  4. customThe reaction was quenched by slowly adding EtOH (60 mL)
  5. extractiona saturated aqueous solution of NH4Cl (200 mL) at 5° C., and extracted with ethyl acetate (3×250 mL)
  6. washThe combined organic extracts were successively washed with water (200 mL) and brine (200 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customFlash chromatography (Biotage, 75-S, 92/8 hexanes/ethyl acetate) purification of the crude oil

Sources & evidence

ORD record
ord-525a2227f3894681988c550c29490ad8
Source dataset
uspto-grants-2003_03
Patent number
US06531598B1

Reaction notes

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