Water → 2-((Trimethylsilyl)ethynyl)nicotinonitrile

HRID 1772012Notes

Reaction equation

HRID 1772012 reaction equation
Cl[C:2]1[N:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C(N(CC)CC)C.[C:17]([Si:19]([CH3:22])([CH3:21])[CH3:20])#[CH:18].O>C1(C)C=CC=CC=1.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].[Cu]I>[CH3:20][Si:19]([C:17]#[C:18][C:2]1[N:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5])([CH3:22])[CH3:21]

Participants

8

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 810792-Chloronicotinonitrile

Product 1

HCID 134111132-((Trimethylsilyl)ethynyl)nicotinonitrileYield 61.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 2-chloronicotinonitrile (21.6 g, 156 mmol) in toluene (200 mL) was added Pd(dppf)Cl2 (2.3 g, 3.12 mmol), copper (I) iodide (594 mg, 3.12 mmol), triethylamine (32 mL, 312 mmol) and ethynyltrimethylsilane (23 g, 234 mmol). The reaction mixture was stirred at 70° C. under N2 for 5 h. The reaction mixture was filtered through a Celite pad. The filtrate was concentrated under reduced pressure to give a residue. 40 mL of water was added to the residue, and the mixture was extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine (1×100 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography (eluting with a gradient of PE/EtOAc v/v 40:1, 20:1, 10:1, 5:1) to yield 2-((trimethylsilyl)ethynyl)nicotinonitrile as a yellow solid (19.14 g, yield 61%). ESI MS: m/z 201 [M+H]+.

Workup

  1. filtrationThe reaction mixture was filtered through a Celite pad
  2. concentrationThe filtrate was concentrated under reduced pressure
  3. customto give a residue
  4. extractionthe mixture was extracted with EtOAc (3×100 mL)
  5. washThe combined organic layers were washed with brine (1×100 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give the crude product
  10. customThe crude product was purified by silica gel column chromatography (
  11. washeluting with a gradient of PE/EtOAc v/v 40:1, 20:1, 10:1, 5:1)

Sources & evidence

ORD record
ord-d883dcf8f6c84536b44d10a2a48d1a1e
Source dataset
uspto-grants-2016_02
Patent number
US09249162B2

Reaction notes

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