Ethylamine → 3-Ethylamino-6-methoxy-2-(methoxymethyloxy)methylpyridine

HRID 906320Notes

Reaction equation

HRID 906320 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+].[CH2:21]([NH2:23])[CH3:22]>O1CCCC1>[CH2:21]([NH:23][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)[CH3:22]

Participants

5

Reactant 3

HCID 6341EthylamineHCID 23676156Sodium t-butoxideHCID 672418193-Bromo-6-methoxy-2-[(methoxymethoxy)methyl]pyridine

Product 1

HCID 672423343-Ethylamino-6-methoxy-2-(methoxymethyloxy)methylpyridineYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-bromo-6-methoxy-2-[(methoxymethoxy)methyl]pyridine (1.50 g, 5.72 mmol), tris(dibenzylideneacetone)(chloroform)dipalladium(0) (592 mg, 0.572 mmol), (2-biphenyl)di-t-butylphosphine (680 mg, 2.28 mmol), sodium t-butoxide (1.65 g, 17.2 mmol) and ethylamine (2.0 M solution in tetrahydrofuran, 15 mL, 30 mmol) in tetrahydrofuran (15 mL) was warmed to 135° C. over 3 minutes under microwave irradiation (500 W). The reaction mixture was cooled, then filtered through Celite, and washed with ethyl acetate. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:1) to obtain N-ethyl-6-methoxy-2-[(methoxymethoxy)methyl]pyridin-3-amine (954 mg, 74%) as yellow oil.

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered through Celite
  3. washwashed with ethyl acetate
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:1)

Sources & evidence

ORD record
ord-d2d3dbe41cd84152a4ee1081c5fd2d98
Source dataset
uspto-grants-2011_09
Patent number
US08012989B2

Reaction notes

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