Diethyl Ether → 3-(1-methyl-1H-pyrrol-2-yl)benzaldehyde

HRID 990526Notes

Reaction equation

HRID 990526 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[CH:3]1.CN([CH2:10][CH2:11]N(C)C)C.[Li][CH2:16][CH2:17][CH2:18][CH3:19].[Sn](Cl)(C)(C)C.[F-].[K+].C[CH2:28][O:29]CC>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C.O1CCOCC1>[CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:16]1[CH:17]=[C:18]([CH:19]=[CH:10][CH:11]=1)[CH:28]=[O:29]

Participants

11

Reactant 6

HCID 3283Diethyl EtherHCID 73041-MethylpyrroleHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 14016Trimethyltin chlorideHCID 522689Potassium FluorideHCID 178418339Butyllithium

Product 1

HCID 235059913-(1-methyl-1H-pyrrol-2-yl)benzaldehydeYield 24%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
-78 °C

Procedure

To solution of N-methylpyrrole (0.97 mL, 11 mmol) in Et2O (20 mL) was added neat TMEDA (1.5 mL, 10 mmol) and 1.6 M n-BuLi in hexanes (6.3 mL, 10 mmol). The solution was heated to reflux under N2 for 1 h and then cooled to −78° C. A 1.0 M solution of Me3SnCl in THF was added over 15 min, and the resulting solution stirred for 30 min at −78° C. After warming to room temperature, 3-bromo-henzaldehyde (0.70 mL, 6.0 mmol), Pd(PPh3)2Cl2 (0.25 g, 0.35 mmol) and dioxane (10 mL) were added. The slurry was heated to reflux for 18 h. The cooled mixture was poured into a mixture of saturated KF and ethyl acetate and stirred 15 min. The slurry was filtered through celite. The organic layer was separated, washed with brine, dried (MgSO4) and evaporated to an oil. Purification by flash chromatography on silica gel eluting with 5% ethyl acetate in hexane gave 0.45 g (24%) of the desired 3-(1-methyl-1H-pyrrol-2-yl)benzaldehyde product as a yellow oil. MS: m/z=186.2 [M+H]+.

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux under N2 for 1 h
  3. temperatureAfter warming to room temperature
  4. temperatureThe slurry was heated
  5. temperatureto reflux for 18 h
  6. stirringstirred 15 min
  7. filtrationThe slurry was filtered through celite
  8. customThe organic layer was separated
  9. washwashed with brine
  10. dry with materialdried (MgSO4)
  11. customevaporated to an oil
  12. customPurification by flash chromatography on silica gel eluting with 5% ethyl acetate in hexane

Sources & evidence

ORD record
ord-fa19a29f884a4578a4825256aacfbfc8
Source dataset
uspto-grants-2002_10
Patent number
US06458852B1

Reaction notes

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