Triethylamine → 2,3-Dichloro-5-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)pyridine

HRID 420757Notes

Reaction equation

HRID 420757 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][OH:10])[CH:5]=[N:6][C:7]=1[Cl:8].CCN(CC)CC.[Si:18](Cl)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]>CN(C=O)C.CC(OC)(C)C.O>[Cl:8][C:7]1[C:2]([Cl:1])=[CH:3][C:4]([CH2:9][O:10][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])=[CH:5][N:6]=1

Participants

7

Reactant 3

HCID 8471Triethylamine2×HCID 28928tert-Butyldimethylsilyl chloride2×HCID 21882961(5,6-Dichloropyridin-3-yl)methanol

Product 1

HCID 866368452,3-Dichloro-5-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)pyridineYield 76.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

A mixture of (5,6-dichloro-3-pyridinyl)methanol (2000 mg, 11.23 mmol), Et3N (2.349 ml, 16.85 mmol), and tert-butyldimethylsilyl chloride (1778 mg, 11.80 mmol) in DMF (20 ml) was stirred at room temperature for 4 h. HPLC analyse showed starting material remaining, an excess of tert-butyldimethylsilyl chloride (847 mg, 5.62 mmol) and Et3N (1.174 ml, 8.43 mmol) were added. The mixture reaction was stirred overnight. The crude was diluted with TBME (175 mL) and water. The organic phase was washed with solution sat. NaCl. Combined organics were washed with sat NH4Cl and dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by flash chromatography using Flashmaster II, a 50 g silica gel cartridge, and mixtures of hexane and EtOAc as eluent afforded 2,3-Dichloro-5-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)pyridine 2.5 g (72%) of a yellow oil.

Workup

  1. customThe mixture reaction
  2. stirringwas stirred overnight
  3. washThe organic phase was washed with solution sat. NaCl
  4. washCombined organics were washed with sat NH4Cl
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash chromatography

Sources & evidence

ORD record
ord-e18a3a642fb048c6be590e5d57d3a3e5
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

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