Anisole → Methyl 2-amino-6-chloronicotinate

HRID 570680Notes

Reaction equation

HRID 570680 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8]CC2C=CC(OC)=CC=2)[C:5]([C:18]([O:20][CH3:21])=[O:19])=[CH:4][CH:3]=1.C1(OC)C=CC=CC=1>FC(F)(F)C(O)=O>[NH2:8][C:6]1[C:5]([C:18]([O:20][CH3:21])=[O:19])=[CH:4][CH:3]=[C:2]([Cl:1])[N:7]=1

Participants

4

Reactant 2

HCID 7519AnisoleHCID 86685350HCID 86685350, compound

Product 1

HCID 57415887Methyl 2-amino-6-chloronicotinateYield 98%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of methyl 6-chloro-2-[(4-methoxybenzyl)amino]pyridine-3-carboxylate (1.0 g) in trifluoroacetic acid (5 ml) was added anisole (0.5 ml), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, and the residue was subjected to azeotropic distillation with toluene. The obtained oil residue was diluted with ethyl acetate (80 ml), and the mixture was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (596 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. distillationthe residue was subjected to azeotropic distillation with toluene
  3. additionThe obtained oil residue was diluted with ethyl acetate (80 ml)
  4. washthe mixture was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9cbcf2abf79446d387cdc2695d051594
Source dataset
uspto-grants-2015_05
Patent number
US09023858B2

Reaction notes

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