Lithium diisopropylamide → HCID 57795084, compound

HRID 2099568Notes

Reaction equation

HRID 2099568 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[CH:28]=[CH:27][CH:26]=[C:25]([CH:29](Cl)[C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([O:36][CH3:37])[N:31]=2)[N:24]=1>C1COCC1>[Br:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH:29]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([O:36][CH3:37])[N:31]=2)[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)[N:24]=1

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 147626403,3'-MethylenedipyridineHCID 86094445HCID 86094445, compound

Product 1

HCID 57795084HCID 57795084, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a mixture of 3-(pyridine-3-ylmethyl)pyridine (2 g, 11.75 mmol) in anhydrous THF (40 mL) @ −78° C. under N2. was added LDA (9.79 mL, 1.8 M) dropwise. The mixture was stirred @ −78° C. for 1 hr and 2-bromo-6-[chloro(6-methoxypyridin-2-yl)methyl]pyridine was added. The mixture was warmed to 0° C. and stirred for 2 hr. The reaction 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 (1-5% MeOH in CH2Cl2) to give 2-bromo-6-[1-(6-methoxypyridin-2-yl)-2,2-dipyridin-3-ylethyl]pyridine. 1H NMR (500 MHz, CDCl3) δ 8.51 (t, 2H, J=2.7), 8.36-8.28 (m, 2H), 7.69 (dt, 1H, J=8.1, 2.0), 7.58 (dt, 1H, J=8.0, 1.9) 7.50 (d, 1H, J=7.6), 7.38-7.30 (m, 2H), 7.18 (d, 1H, J=7.8), 7.13 (dd, 1H, J=7.9, 4.8), 7.09 (dd, 1H, J=7.8, 4.9), 6.86 (d, 1H, J=7.3), 6.45 (d, 1H, J=8.1), 5.27 (d, 1H, J=12.2), 5.06 (d, 1H, J=12.5), 3.95 (s, 3H), LRMS m/z (M+H) Calcd.: 447.1, found: 447.1. The racemic mixture was separated by ChiralPak AD (40% EtOH in Hexanes+DEA 1 mL/L). The first peak was enantiomer A of 2-bromo-6-[1-(6-methoxypyridin-2-yl)-2,2-dipyridin-3-ylethyl]pyridine, and the second peak was enantiomer B of 2-bromo-6-[1-(6-methoxypyridin-2-yl)-2,2-dipyridin-3-ylethyl]pyridine.

Workup

  1. custom@ −78° C. under N2
  2. temperatureThe mixture was warmed to 0° C.
  3. stirringstirred for 2 hr
  4. customThe reaction 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 (1-5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-30bae40e87da439483a175341417792b
Source dataset
uspto-grants-2009_08
Patent number
US07569589B2

Reaction notes

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