Lithium diisopropylamide → Racemic 3-[1-(6-bromopyridin-2-yl)-2,2-dipyridin-3-ylethyl]benzonitrile

HRID 2099565Notes

Reaction equation

HRID 2099565 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:2]=1.[Li+].CC([N-]C(C)C)C.[Br:22][C:23]1[N:28]=[C:27]([CH:29](Cl)[C:30]2[CH:31]=[C:32]([CH:35]=[CH:36][CH:37]=2)[C:33]#[N:34])[CH:26]=[CH:25][CH:24]=1>C1COCC1>[Br:22][C:23]1[N:28]=[C:27]([CH:29]([C:30]2[CH:31]=[C:32]([CH:35]=[CH:36][CH:37]=2)[C:33]#[N:34])[CH:7]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 147626403,3'-MethylenedipyridineHCID 860944363-[(6-Bromopyridin-2-yl)(chloro)methyl]benzonitrile

Product 1

HCID 86094439Racemic 3-[1-(6-bromopyridin-2-yl)-2,2-dipyridin-3-ylethyl]benzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a mixture of 3-(pyridine-3-ylmethyl)pyridine (0.700 g, 4.11 mmol) in anhydrous THF (20 mL) @ −78° C. under N2 was added LDA (3.43 mL, 1.8 M) dropwise. The mixture was stirred for 1 hr @ −78° C., and 3-[(6-bromopyridin-2-yl)(chloro)methyl]benzonitrile was added. The reaction was warmed to 0° C., and stirred for 2 hr. The resulting mixture was quenched with saturated aqueous NH4Cl, and extracted 3× with EtOAc. The combined organics were dried (anhd. Na2SO4), filtered, and concentrated. The residue was purified by silica gel chromatography (1-4% MeOH in CH2Cl2) to give racemic 3-[1-(6-bromopyridin-2-yl)-2,2-dipyridin-3-ylethyl]benzonitrile. LRMS m/z (M+H) Calcd.: 441.0, found: 441.0. The racemic mixture was separated by ChiralPak AD (40% iPrOH in Hexanes+1 mL/L DEA to 80% iPrOH in Hexanes+1 mL/L DEA over 45 min). The first peak was enantiomer A of 3-[1-(6-bromopyridin-2-yl)-2,2-dipyridin-3-ylethyl]benzonitrile, and the second peak was enantiomer B of 3-[1-(6-bromopyridin-2-yl)-2,2-dipyridin-3-ylethyl]benzonitrile.

Workup

  1. custom@ −78° C. under N2
  2. temperatureThe reaction was warmed to 0° C.
  3. stirringstirred for 2 hr
  4. customThe resulting mixture was quenched with saturated aqueous NH4Cl
  5. extractionextracted 3× with EtOAc
  6. dry with materialThe combined organics were dried (anhd. Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography (1-4% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-e53b2459e4d54a28bb7bff93194ead88
Source dataset
uspto-grants-2009_08
Patent number
US07569589B2

Reaction notes

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