Lithium diisopropylamide → HCID 57795056, compound

HRID 2099562Notes

Reaction equation

HRID 2099562 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][C:33]([F:36])=[CH:32][CH: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][C:33]([F:36])=[CH:32][CH: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 860944222-Bromo-6-[chloro(4-fluorophenyl)methyl]pyridine

Product 1

HCID 57795056HCID 57795056, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-(pyridine-3-ylmethyl)pyridine (2.5 g, 14.69 mmol) in anhydrous THF (75 mL) under N2. The mixture was cooled to −78° C. and LDA (12.24 mL, 1.8 M) was added dropwise. The mixture was stirred @ −78° C. for 1 hr and 2-bromo-6-[chloro(4-fluorophenyl)methyl]pyridine (4.64 g, 15.42 mmol) 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 resulting residue was purified by silica gel chromatography (1-3% MeOH in CH2Cl2) to give 2-bromo-6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridine. 1H NMR (500 MHz, CDCl3) δ 8.55 (d, 1H, J=2.0), 8.45 (d, 1H, J=2.0), 8.35-8.29 (m, 2H), 7.60 (dt, 1H, J=7.9, 1.9), 7.49 (dt, 1H, J=7.9, 1.9), 7.35-7.24 (m, 3H), 7.17 (d, 1H, J=7.8), 7.14-7.07 (m, 2H), 7.05 (d, 1H, J=7.6), 6.86 (t, 2H, J=8.7), 5.13 (d, 1H, J=12.2), 4.78 (d, 1H, J=12.0) LRMS m/z (M+H) Calcd.: 434.0, found: 434.0. The racemic mixture was separated by ChiralPak AD (30% iPrOH in Hexane+DEA 1 mL/L). The first peak was enantiomer A of 2-bromo-6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridine; HRMS m/z (M+H) Calcd.: 434.0663, found: 434.0648. And the second peak was enantiomer B of 2-bromo-6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridine; HRMS m/z (M+H) Calcd.: 434.0633, found: 434.0646.

Workup

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

Sources & evidence

ORD record
ord-3523df130e16481ea3c4b85a2dda8767
Source dataset
uspto-grants-2009_08
Patent number
US07569589B2

Reaction notes

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