HCID 86715526, compound → HCID 86715525, compound

HRID 2284609Notes

Reaction equation

HRID 2284609 reaction equation
[CH3:1][Mg+].[Br-].[N:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)[C:5]=1[C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[C:21](=O)[CH2:20][CH2:19]2>C1COCC1>[CH3:1][C:21]1[C:22]2[C:18](=[CH:17][C:16]([C:5]3[C:6]([C:10]4[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=4)=[CH:7][CH:8]=[CH:9][N:4]=3)=[CH:24][CH:23]=2)[CH2:19][CH:20]=1

Participants

4

Reactant 2

HCID 86715526HCID 86715526, compoundHCID 178418689HCID 178418689, compound2×

Product 1

HCID 86715525HCID 86715525, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

MeMgBr [2 mL, 1.4 M solution in toluene/THF (75:25)] was added to a stirring solution of 5-([3,4′-bipyridin]-2-yl)-2,3-dihydro-1H-inden-1-one (175 mg) in THF (4 mL) at −78° C. under argon. The reaction was stirred for 30 min and warmed to room temperature after complete addition of MeMgBr and. After 1 h, the complete consumption of 5-([3,4′-bipyridin]-2-yl)-2,3-dihydro-1H-inden-1-one to 5-([3,4′-bipyridin]-2-yl)-1-methyl-2,3-dihydro-1H-inden-1-ol was observed. Subsequently, the reaction was cooled in ice-bath, quenched with conc. HCl (5 mL) over a period of 30 min. The cooling was removed and allowed the reaction to warm to temperature. After 4 h, the reaction mixture was concentrated, diluted with EtOAc (50 mL) and aq. NaHCO3 solution (15 mL). Aqueous layer was discarded, washed the organic layer with brine, dried over MgSO4, filtered, concentrated and purified by flash column chromatography (Combiflash® companion System® with RediSep® silica gel column 12 g, 30-50-70% EtOAc/hexanes as an eluting solvent) to obtain 2-(3-Methyl-1H-inden-6-yl)-3,4′-bipyridine as an oil. LCMS: rt 4.47 min (A), purity 95%, MS (m/e) 285 (MH+).

Workup

  1. waitAfter 1 h
  2. customthe complete consumption of 5-([3,4′-bipyridin]-2-yl)-2,3-dihydro-1H-inden-1-one to 5-([3,4′-bipyridin]-2-yl)-1-methyl-2,3-dihydro-1H-inden-1-ol
  3. temperatureSubsequently, the reaction was cooled in ice-bath
  4. customquenched with conc. HCl (5 mL) over a period of 30 min
  5. customThe cooling was removed
  6. customthe reaction
  7. temperatureto warm to temperature
  8. waitAfter 4 h
  9. concentrationthe reaction mixture was concentrated
  10. additiondiluted with EtOAc (50 mL) and aq. NaHCO3 solution (15 mL)
  11. washwashed the organic layer with brine
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. custompurified by flash column chromatography (Combiflash® companion System® with RediSep® silica gel column 12 g, 30-50-70% EtOAc/hexanes as an eluting solvent)

Sources & evidence

ORD record
ord-e49dce8af7934b7ab26fa95379c7e4ea
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

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