3-Bromopyridine → 3-(2,5-Dimethoxy-3,4,6-trimethylbenzyl)pyridine

HRID 232074Notes

Reaction equation

HRID 232074 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.C([Li])CCC.[CH3:13][O:14][C:15]1[C:22]([CH3:23])=[C:21]([CH3:24])[C:20]([O:25][CH3:26])=[C:19]([CH3:27])[C:16]=1[CH2:17]Br>C(OCC)C.O>[CH3:26][O:25][C:20]1[C:21]([CH3:24])=[C:22]([CH3:23])[C:15]([O:14][CH3:13])=[C:16]([CH3:17])[C:19]=1[CH2:27][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 122863-BromopyridineHCID 142777601-(Bromomethyl)-2,5-dimethoxy-3,4,6-trimethylbenzeneHCID 178418339Butyllithium

Product 1

HCID 145762633-(2,5-Dimethoxy-3,4,6-trimethylbenzyl)pyridineYield 85.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×

Procedure

A solution of 15.5 g (98.1 mmol) of 3-bromopyridine in 200 ml of ethyl ether was cooled to -78° C., to which 61.3 ml (98.1 mmol) of n-butyllithium (1.6M hexane solution) was added dropwise. For 20 minutes after completion of the addition, the mixture was stirred at the same temperature, and then a solution of 26.8 g (98.1 mmol) of 2,5-dimethoxy-3,4,6-trimethylbenzyl bromide in 100 ml of ethyl ether was added dropwise. After stirring at -78° C. to room temperature for 1 hour, the reaction mixture was diluted with water and extracted with ethyl acetate. Then the extract was extracted reversely with 2N-hydrochloric acid, and the water layer was made weakly alkaline with a saturated aqueous solution of sodium hydrogen carbonate and extracted with ethyl acetate. The extract was washed with water, dried, and concentrated. The residue was purified with silica gel column chromatography (ethyl acetate), to give 22.8 g (85.8%) of 3-(2,5-dimethoxy- 3,4,6-trimethylbenzyl)pyridine.

Workup

  1. additionwas added dropwise
  2. additionFor 20 minutes after completion of the addition
  3. stirringAfter stirring at -78° C. to room temperature for 1 hour
  4. extractionextracted with ethyl acetate
  5. extractionThen the extract was extracted reversely with 2N-hydrochloric acid
  6. extractionextracted with ethyl acetate
  7. washThe extract was washed with water
  8. customdried
  9. concentrationconcentrated
  10. customThe residue was purified with silica gel column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-0ae9b07e0b0a4576923b1accd7abfbb1
Source dataset
uspto-grants-1989_07
Patent number
US04851413

Reaction notes

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