Methanol → 2-[(Tert-butyldimethylsilanyl)ethynyl]-5-(4-chlorophenyl)pyridine

HRID 2112812Notes

Reaction equation

HRID 2112812 reaction equation
CO.C(=O)([O-])[O-].[Na+].[Na+].Br[C:10]1[CH:11]=[CH:12][C:13]([C:16]#[C:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])=[N:14][CH:15]=1.[Cl:25][C:26]1[CH:31]=[CH:30][C:29](OB(O)O)=[CH:28][CH:27]=1>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Si:18]([C:17]#[C:16][C:13]1[CH:12]=[CH:11][C:10]([C:29]2[CH:30]=[CH:31][C:26]([Cl:25])=[CH:27][CH:28]=2)=[CH:15][N:14]=1)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]

Participants

7

Reactant 4

HCID 887MethanolHCID 10340Sodium CarbonateHCID 17810664p-Chlorophenylboric acidHCID 666112135-Bromo-2-((tert-butyldimethylsilyl)ethynyl)pyridine

Product 1

HCID 690583502-[(Tert-butyldimethylsilanyl)ethynyl]-5-(4-chlorophenyl)pyridine

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

250 mL of MeOH, 220 mL of 2N sodium carbonate (Na2CO3) solution, and 1.80 g (2.46 mmol) of PdCl2(dppf) are added to a solution of 59.5 g (201.0 mmol) of 5-bromo-2-[(tert-butyldimethylsilanyl)ethynyl]pyridine and 36.5 g (233.4 mmol) of 4-chlorophenylboric acid in 600 mL of 1,4-dioxane and the mixture is refluxed for 1 hour. The reaction mixture is evaporated down in vacuo and diluted with EtOAc. The organic phase is washed with water and semisaturated sodium bicarbonate (NaHCO3) solution, dried over sodium sulfate, and evaporated down in vacuo. The residue is purified by column chromatography (silica gel, Cyc/EtOAc 9:1). Yield: 38.5 g (58% of theoretical); C19H22ClNSi (M=327.923); calc.: molpeak (M+H)+: 328/330 (Cl); found: molpeak (M+H)+: 328/330 (Cl); Rf value: 0.60 (silica gel, Cyc/EtOAc 8:1).

Workup

  1. temperaturethe mixture is refluxed for 1 hour
  2. customThe reaction mixture is evaporated down in vacuo
  3. additiondiluted with EtOAc
  4. washThe organic phase is washed with water and semisaturated sodium bicarbonate (NaHCO3) solution
  5. dry with materialdried over sodium sulfate
  6. customevaporated down in vacuo
  7. customThe residue is purified by column chromatography (silica gel, Cyc/EtOAc 9:1)

Sources & evidence

ORD record
ord-a474e408b4464b59b5097214d30633bc
Source dataset
uspto-grants-2009_04
Patent number
US07524862B2

Reaction notes

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