Trimethylsilylacetylene → 2-Chloro-6-(hydroxymethyl)-4-[2-(trimethylsilyl)ethynyl]pyridin-3-ol

HRID 1830532Notes

Reaction equation

HRID 1830532 reaction equation
[Cl:1][C:2]1[C:7]([OH:8])=[C:6](I)[CH:5]=[C:4]([CH2:10][OH:11])[N:3]=1.[CH3:12][Si:13]([C:16]#[CH:17])([CH3:15])[CH3:14]>C(Cl)(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[C:7]([OH:8])=[C:6]([C:17]#[C:16][Si:13]([CH3:15])([CH3:14])[CH3:12])[CH:5]=[C:4]([CH2:10][OH:11])[N:3]=1

Participants

5

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 106845682-Chloro-6-(hydroxymethyl)-4-iodo-3-pyridinol

Product 1

HCID 105152062-Chloro-6-(hydroxymethyl)-4-[2-(trimethylsilyl)ethynyl]pyridin-3-olYield 92%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6212ChloroformSolvent2×

Procedure

C2 (13.9 g, 48.6 mmol) is combined with trimethylsilylacetylene (9.6 mL, 68 mmol), bis(triphenylphosphine)palladium dichloride (1.02 g, 1.46 mmol) and cuprous iodide (139 mg, 0.73 mmol) in 80 mL CHCl3/40 mL THF under N2. TEA (21 mL, 151 mmol) is added, and the reaction is stirred 3 h at rt and is diluted with 200 mL CHCl3. The mixture is washed with 2×150 mL 5% HCl and the combined aqueous layers are extracted with 2×50 mL CHCl3. The combined organic layer is washed with 100 mL 50% saturated NaCl, is dried over anhydrous MgSO4, and is concentrated in vacuo to an amber oil. The crude material is chromatographed over 350 g silica gel (230–400 mesh), eluting with 35% EtOAc/hexane. The fractions with the desired compound are combined and concentrated to afford 2-chloro-6-(hydroxymethyl)-4-[(trimethylsilyl)ethynyl]-3-pyridinol (C3) as a golden solid (92% yield). MS (EI) for C11H14ClNO2Si, m/z: 255(M)+.

Workup

  1. washThe mixture is washed with 2×150 mL 5% HCl
  2. extractionthe combined aqueous layers are extracted with 2×50 mL CHCl3
  3. washThe combined organic layer is washed with 100 mL 50% saturated NaCl
  4. dry with materialis dried over anhydrous MgSO4
  5. concentrationis concentrated in vacuo to an amber oil
  6. customThe crude material is chromatographed over 350 g silica gel (230–400 mesh)
  7. washeluting with 35% EtOAc/hexane
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-2d3d70f6c08841889d4a351a68370258
Source dataset
uspto-grants-2006_06
Patent number
US07067515B2

Reaction notes

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