Pyrrolidine → 6-Methoxy-2-(methoxymethyloxy)methyl-3-(pyrrolidin-1-yl)pyridine

HRID 2353333Notes

Reaction equation

HRID 2353333 reaction equation
Br[C:2]1[C:3]([CH2:10][O:11][CH2:12][O:13][CH3:14])=[N:4][C:5]([O:8][CH3:9])=[CH:6][CH:7]=1.CC(C)([O-])C.[Na+].[NH:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1>C1(C)C=CC=CC=1>[CH3:9][O:8][C:5]1[N:4]=[C:3]([CH2:10][O:11][CH2:12][O:13][CH3:14])[C:2]([N:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=[CH:7][CH:6]=1

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 23676156Sodium t-butoxideHCID 672418193-Bromo-6-methoxy-2-[(methoxymethoxy)methyl]pyridine

Product 1

HCID 684505796-Methoxy-2-(methoxymethyloxy)methyl-3-(pyrrolidin-1-yl)pyridineYield 14%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 3-bromo-6-methoxy-2-(methoxymethyloxy)methylpyridine (324.6 mg, 1.24 mmol), tris(dibenzylideneacetone)(chloroform)dipalladium(0) (32.7 mg, 0.03 mmol), (2-biphenyl)di-t-butylphosphine (18.5 mg, 0.06 mmol), sodium t-butoxide (357 mg, 3.71 mmol) and pyrrolidine (640 mg, 3.74 mmol) in toluene (4.5 mL) was stirred at 135° C. for 3 hours in a sealed tube. The reaction mixture was extracted with chloroform/water, and the organic layer was washed with saturated brine, then dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by preparative silica gel thin layer chromatography (hexane:ethyl acetate=3:1) to obtain 6-methoxy-2-(methoxymethyloxy)methyl-3-(pyrrolidin-1-yl)pyridine (42.7 mg, 14%) as yellow oil.

Workup

  1. extractionThe reaction mixture was extracted with chloroform/water
  2. washthe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by preparative silica gel thin layer chromatography (hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-ebf633a387c547c39eb3b2bb07199b86
Source dataset
uspto-grants-2010_07
Patent number
US07750019B2

Reaction notes

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