Citric Acid → 2-(4-Piperidin-1-yl-but-1-ynyl)-6-piperidin-1-ylmethyl-pyridine

HRID 551592Notes

Reaction equation

HRID 551592 reaction equation
Br[C:2]1[N:7]=[C:6]([CH:8]=O)[CH:5]=[CH:4][CH:3]=1.[Li][CH2:11][CH2:12][CH2:13][CH3:14].[CH2:15]([Mg]Cl)[CH2:16][CH2:17][CH3:18].Br[C:22]1C=[CH:26][CH:25]=[C:24](Br)[N:23]=1.[CH3:29][N:30](C=O)[CH3:31].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1(C)C=CC=CC=1.O>[N:23]1([CH2:24][CH2:25][C:26]#[C:8][C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([CH2:29][N:30]3[CH2:31][CH2:18][CH2:17][CH2:16][CH2:15]3)[N:7]=2)[CH2:22][CH2:14][CH2:13][CH2:12][CH2:11]1

Participants

9

Reactant 6

HCID 311Citric AcidHCID 6228DimethylformamideHCID 122742,6-DibromopyridineHCID 27570096-Bromopyridine-2-carbaldehydeHCID 178418265HCID 178418265, compoundHCID 178418339Butyllithium

Product 1

HCID 115804372-(4-Piperidin-1-yl-but-1-ynyl)-6-piperidin-1-ylmethyl-pyridineYield 52%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent3×

Conditions

Temperature
-10 °C

Procedure

6-Bromo-pyridine-2-carbaldehyde. To a −10° C. solution of n-BuLi (2.5 M in hexane, 5.6 mL, 14 mmol) in anhydrous toluene (20 mL) was added a solution of n-BuMgCl (2 M in THF, 3.5 mL) over 20 min, maintaining the temperature between −10° C. and 0° C. The mixture was stirred at −10° C. for 30 min. A solution of 2,6-dibromo-pyridine (4.74 g, 20 mmol) in toluene (20 mL) was added drop-wise over a period of 30 min while keeping the temperature below −5° C. The resulting suspension was stirred at −10° C. for 2.5 h. The mixture was transferred via cannula to a −10° C. solution of DMF (1.9 g, 26 mmol) in toluene (10 mL). The solution was allowed to stand between −5° C. and −10° C. for 30 min and then was transferred into a solution of citric acid (8.00 g) in H2O (15 mL), maintaining the temperature below 20° C. The resulting solution was stirred for 10 min and the layers were separated. The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified (SiO2: 10% ethyl acetate/hexanes) to afford the title compound (1.94 g, 52%).

Workup

  1. temperaturemaintaining the temperature between −10° C. and 0° C
  2. customthe temperature below −5° C
  3. stirringThe resulting suspension was stirred at −10° C. for 2.5 h
  4. customwas transferred via cannula to a −10° C.
  5. waitto stand between −5° C. and −10° C. for 30 min
  6. temperaturemaintaining the temperature below 20° C
  7. stirringThe resulting solution was stirred for 10 min
  8. customthe layers were separated
  9. dry with materialThe organic layer was dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified (SiO2: 10% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-0ea6c8f8330e4278b98642b614e4ccff
Source dataset
uspto-grants-2011_05
Patent number
US07947718B2

Reaction notes

Loading…