Propanal → 1-[6-(2,5-Dimethylpyrrol-1-yl)pyridin-3-yl]propan-1-ol

HRID 600630Notes

Reaction equation

HRID 600630 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([CH3:13])=[CH:11][CH:10]=[C:9]2[CH3:14])=[N:6][CH:7]=1.C([Li])CCC.[CH:20](=[O:23])[CH2:21][CH3:22].O>COC(C)(C)C.CCCCCC>[CH3:14][C:9]1[N:8]([C:5]2[N:6]=[CH:7][C:2]([CH:20]([OH:23])[CH2:21][CH3:22])=[CH:3][CH:4]=2)[C:12]([CH3:13])=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 527PropanalHCID 962WaterHCID 120436225-Bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)pyridineHCID 178418339Butyllithium

Product 1

HCID 672732841-[6-(2,5-Dimethylpyrrol-1-yl)pyridin-3-yl]propan-1-olYield 58.3%

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 15413tert-Butyl methyl etherSolvent2×

Conditions

Temperature
-70 °C

Procedure

To a solution of 2 g of 5-bromo-2-(2,5-dimethylpyrrol-1-yl)pyridine in 30 mL of tert-butyl methyl ether cooled to −78° C. are added slowly, under argon, 3.3 mL of a 2.5M solution of butyllithium in hexane, the mixture is then stirred for 40 minutes at about −70° C., followed by addition of a solution of 0.5 g of propionaldehyde in 5 mL of tert-butyl methyl ether. The mixture is stirred for 30 minutes at about −70° C., 20 mL of water are then added slowly and the resulting mixture is allowed to warm to 20° C. The aqueous phase is extracted with twice 100 mL of ethyl acetate and the organic phases are combined, dried and concentrated to dryness. The residue is purified by flash chromatography on a cartridge of 70 g of silica, eluting with dichloromethane and then with an 80/20 mixture of dichloromethane and ethyl acetate. The fractions containing the expected product are combined and concentrated under vacuum to give 1.07 g of 1-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]propan-1-ol in the form of a yellow oil.

Workup

  1. additionare added slowly, under argon
  2. temperatureto warm to 20° C
  3. extractionThe aqueous phase is extracted with twice 100 mL of ethyl acetate
  4. customdried
  5. concentrationconcentrated to dryness
  6. customThe residue is purified by flash chromatography on a cartridge of 70 g of silica
  7. washeluting with dichloromethane
  8. additionwith an 80/20 mixture of dichloromethane and ethyl acetate
  9. additionThe fractions containing the expected product
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-1932acdff0bd4f5787672876e7253a2f
Source dataset
uspto-grants-2011_03
Patent number
US07902219B2

Reaction notes

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