Triethylamine → 6-Methoxy-2,5-dimethylpyridin-3-amine

HRID 2088508Notes

Reaction equation

HRID 2088508 reaction equation
Br[CH:2](Br)[C:3]1[C:8]([N+:9]([O-])=O)=[CH:7][C:6]([CH3:12])=[C:5]([O:13][CH3:14])[N:4]=1.C(N(CC)CC)C>CCO.[Pd]>[CH3:14][O:13][C:5]1[N:4]=[C:3]([CH3:2])[C:8]([NH2:9])=[CH:7][C:6]=1[CH3:12]

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 445964852-(Dibromomethyl)-6-methoxy-5-methyl-3-nitropyridine

Product 1

HCID 445964866-Methoxy-2,5-dimethylpyridin-3-amineYield 73%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution of 2-(dibromomethyl)-6-methoxy-5-methyl-3-nitropyridine (110 g, 0.323 mol) from Part J, in EtOH (1.1 L) in a Parr bottle was added triethylamine (135 mL, 0.970 mol) followed by 10% Pd/C (11.0 g). The mixture placed on a Parr shaker under an H2 atm at 45 psi for 18 h. The reaction mixture was filtered through Celite and the filtrate was concentrated. The residue was partitioned between water and EtOAc and the organic layer was washed with water, brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (10%→20%→35%→50% ethyl acetate in hexanes) to give 6-methoxy-2,5-dimethylpyridin-3-amine (35.7 g, 73% yield) as a light-brown solid: mp 39.8-41° C.; 1H NMR (400 mHz, DMSO-d6) δ 6.82 (s, 1H), 4.37 (s, 2H), 3.73 (s, 3H), 2.16 (s, 3H), 2.00 (s, 3H); 13C NMR (100 mHz, DMSO-d6) δ 152.7, 135.8, 134.8, 126.3, 116.1, 52.1, 19.2, 14.7; LRMS, (ESI) m/e 153.2 [(M+H)+, calcd for C8H13N2O, 153.1].

Workup

  1. customfor 18 h
  2. filtrationThe reaction mixture was filtered through Celite
  3. concentrationthe filtrate was concentrated
  4. customThe residue was partitioned between water and EtOAc
  5. washthe organic layer was washed with water, brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography on silica gel (10%→20%→35%→50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-f69c88d7246d462ab90c02b7319446b0
Source dataset
uspto-grants-2013_05
Patent number
US08436000B2

Reaction notes

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