Pentane → 3-Ethynyl-4-methoxypyridine

HRID 593571Notes

Reaction equation

HRID 593571 reaction equation
Br[C:2](Br)=[CH:3][C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:9]=1[O:10][CH3:11].[Li]CCCC.CCCCC.[NH4+].[Cl-]>O.C1COCC1>[CH3:11][O:10][C:9]1[CH:8]=[CH:7][N:6]=[CH:5][C:4]=1[C:3]#[CH:2]

Participants

7

Reactant 4

HCID 8003PentaneHCID 25517Ammonium ChlorideHCID 582155483-(2,2-Dibromo-vinyl)-4-methoxy-pyridineHCID 178418339Butyllithium

Product 1

HCID 582157063-Ethynyl-4-methoxypyridine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A flask is charged with 3-(2,2-dibromo-vinyl)-4-methoxy-pyridine (3.7 g, 12.63 mmol) and THF (100 mL), and 1.6 M nBuLi in pentane (17.4 mL, 27.79 mmol) is added dropwise at −78° C. The mixture is stirred at −78° C. for 1 h before addition of saturated aqueous NH4Cl (0.5 mL). The mixture is warmed to room temperature and poured into water (100 mL). The mixture is extracted with ethyl acetate and the combined organic phase is dried over Na2SO4. Concentration followed by silica gel flash chromatography eluting with a 0 to 5% methanol-dichloromethane gradient gives 4-methoxy-3-ethynyl-pyridine. 1H NMR (400 MHz, CDCl3) δ ppm 3.39 (s, 1H), 3.96 (s, 3H), 6.82 (d, J=5.8 Hz, 1H), 8.46 (d, J=5.8 Hz, 1H), 8.58 (s, 1H).

Workup

  1. additionis added dropwise at −78° C
  2. extractionThe mixture is extracted with ethyl acetate
  3. dry with materialthe combined organic phase is dried over Na2SO4
  4. concentrationConcentration
  5. washeluting with a 0 to 5% methanol-dichloromethane gradient

Sources & evidence

ORD record
ord-fcabebed6b664c80a400d0571571aa02
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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