Imidazole → 4-(Tert-butyldimethylsilyloxymethyl)pyridine

HRID 1963115Notes

Reaction equation

HRID 1963115 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH2:7][OH:8])=[CH:3][CH:2]=1.N1C=CN=C1.[CH3:14][C:15]([Si:18](Cl)([CH3:20])[CH3:19])([CH3:17])[CH3:16]>CN(C=O)C.C(Cl)Cl>[Si:18]([O:8][CH2:7][C:4]1[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=1)([C:15]([CH3:17])([CH3:16])[CH3:14])([CH3:20])[CH3:19]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 114724-HydroxymethylpyridineHCID 28928tert-Butyldimethylsilyl chloride

Product 1

HCID 109878804-(Tert-butyldimethylsilyloxymethyl)pyridineYield 98%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of pyridin-4-ylmethanol (25.7 g, 0.24 mol) and imidazole (19.8 g, 0.29 mol) in dry DMF (300 mL) and dry DCM (33 mL) under nitrogen atmosphere was added TBDMSCl (42.6 g, 0.29 mol). The solution was stirred for 18 h under which time a precipitate formed. The reaction mixture was concentrated by removal of volatiles (about 100 mL) followed by addition of water (500 mL). The resulting mixture was extracted with 1:1 heptane:EtOAc (200 mL×3). The combined organic phases were washed with brine (×2), dried (MgSO4), filtered and evaporated to yield 4-((tert-butyldimethylsilyloxy)-methyl)pyridine (51.70 g, 98%) as an oil. 1H NMR (600 MHz, cdcl3) δ −0.01 (s, 6H), 0.82 (s, 9H), 4.63 (s, 2H), 7.14 (m, 2H), 8.43 (m, 2H).

Workup

  1. customformed
  2. concentrationThe reaction mixture was concentrated by removal of volatiles (about 100 mL)
  3. additionfollowed by addition of water (500 mL)
  4. extractionThe resulting mixture was extracted with 1:1 heptane
  5. washThe combined organic phases were washed with brine (×2)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-7c1bab39734a47238b5c75870d59244b
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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