Imidazole → 4-(((tert-Butyldimethylsilyl)oxy)methyl)-2-chloro-6-methoxypyridine

HRID 15347

Reaction equation

HRID 15347 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][OH:9])[CH:5]=[C:4]([O:10][CH3:11])[N:3]=1.[Si:12](Cl)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].N1C=CN=C1.O>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][O:9][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])[CH:5]=[C:4]([O:10][CH3:11])[N:3]=1

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 28928tert-Butyldimethylsilyl chlorideHCID 11457961(2-Chloro-6-methoxypyridin-4-yl)methanol

Product 1

HCID 574868884-(((tert-Butyldimethylsilyl)oxy)methyl)-2-chloro-6-methoxypyridineYield 93%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of [2-chloro-6-(methyloxy)-4-pyridinyl]methanol (for a synthesis see Adamczyk, M.; Akireddy, S. R.; Reddy, Rajarathnam E. Tetrahedron 2002, 58(34), 6951)(8.02 g, 46.22 mmol) in dry DMF (100 ml) was treated with tert-butyldimethylsilyl chloride (8.36 g, 55.46 mmol) and imidazole (3.77 g, 55.46 mmol) and stirred at rt for 2 h. The reaction mixture was treated with water extracted three times with dichloromethane, dried (magnesium sulphate), evaporated and chromatographed on silica gel (100 g), eluting with 1:4 ethyl acetate-hexane to give the desired product (12.38 g, 93%).

Workup

  1. extractionextracted three times with dichloromethane
  2. dry with materialdried (magnesium sulphate)
  3. customevaporated
  4. customchromatographed on silica gel (100 g)
  5. washeluting with 1:4 ethyl acetate-hexane

Sources & evidence

ORD record
ord-882eac7cbb6649c0b1d8d9439948d79d
Source dataset
uspto-grants-2010_06
Patent number
US07732461B2

Linked notes

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