Benzaldehyde → HCID 86599704, compound

HRID 2116916Notes

Reaction equation

HRID 2116916 reaction equation
C([Mg]Cl)CCC.C([Li])CCC.Br[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[N:14]=1.[CH:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O1CCCC1.CCCCCC.C1(C)C=CC=CC=1.C(O)(=O)C>[Br:19][C:15]1[N:14]=[C:13]([C:21]2([CH:22]=[CH:23][CH:24]=[CH:25][CH2:26]2)[CH2:20][OH:27])[CH:18]=[CH:17][CH:16]=1

Participants

9

Reactant 4

HCID 240BenzaldehydeHCID 122742,6-DibromopyridineHCID 178418265HCID 178418265, compoundHCID 178418339Butyllithium

Product 1

HCID 86599704HCID 86599704, compoundYield 97%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

n-Butylmagnesium chloride (3.49 mmol) in 2.05M tetrahydrofuran solution (1.70 mL) was added to ice-cooled n-butyllithium (7.03 mmol) in 1.45M hexane solution (4.85 mL) (“Hexanes”, Product of Wako Pure and Chemical Industries, Ltd. The solvent was used in the same way in the working examples hereinafter described). The mixture was stirred at 0° C. for 15 minutes, and then cooled to −10° C. to give a suspension. 2,6-Dibromopyridine (2.37 g, 10.0 mmol) in toluene (25 mL) was added to the suspension below −5° C. over a period of 10 minutes or more. The mixture was stirred at −10° C. for 2 hours, and then benzaldehyde (1.35 ml, 13.3 mmol) was added. After stirring at 0° C. for one hour, 1M acetic acid solution (15 mL) was added. The organic phase was separated, and the aqueous phase was extracted twice with ethyl acetate (10 mL). The organic extracts were combined, washed with an aqueous saturated solution (10 mL) of sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure to remove the solvent. The resultant residue was purified by flash column chromatography on silica gel in a developing solvent system of hexane-ethyl acetate (15:1, v/v) to give the title compound (2.56 g) in 97% yield as a pale yellowish viscous oil.

Workup

  1. temperaturecooled to −10° C.
  2. customto give a suspension
  3. stirringThe mixture was stirred at −10° C. for 2 hours
  4. stirringAfter stirring at 0° C. for one hour
  5. customThe organic phase was separated
  6. extractionthe aqueous phase was extracted twice with ethyl acetate (10 mL)
  7. washwashed with an aqueous saturated solution (10 mL) of sodium chloride
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customto remove the solvent
  11. customThe resultant residue was purified by flash column chromatography on silica gel in a developing solvent system of hexane-ethyl acetate (15:1

Sources & evidence

ORD record
ord-c4f5aa963c8c46c9a2727d9ad89e1957
Source dataset
uspto-grants-2008_10
Patent number
US07439535B2

Reaction notes

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