Sodium Methoxide → 3-fluoro-6-methoxy-N-((4-methyltetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine

HRID 1963896Notes

Reaction equation

HRID 1963896 reaction equation
[F:1][C:2]1[C:3]([NH:9][CH2:10][C:11]2([CH3:17])[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[N:4][C:5](F)=[CH:6][CH:7]=1.[CH3:18][O-:19].[Na+]>CO>[F:1][C:2]1[C:3]([NH:9][CH2:10][C:11]2([CH3:17])[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[N:4][C:5]([O:19][CH3:18])=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 66937075HCID 66937075, compound

Product 1

HCID 669370553-fluoro-6-methoxy-N-((4-methyltetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3,6-difluoro-N-((4-methyltetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine (1.4 g, 5.78 mmol) in MeOH (14 mL) was added sodium methoxide (25 wt. % in MeOH, 7 mL, 30.8 mmol). The mixture was heated in a steel bomb at 135° C. for 3 days. The mixture was cooled to ambient temperature and concentrated in vacuo. The resulting residue was taken up in water (200 mL), and the resulting precipitate was filtered off and rinsed with water. The solid was dissolved in DCM. The organic solution was washed with brine, dried over Na2SO4, filtered off and concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, 80 g, 20 min, EtOAc/heptane= 0/100 for 2 min, then EtOAc/heptane= 5/95 to 25/75 over 23 min, EtOAc/heptane= 25/75] providing 3-fluoro-6-methoxy-N-((4-methyltetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine as an off-white solid. Yield: 1.22 g. LCMS (m/z): 255.1 [M+H]+; Retention time=0.89 min.

Workup

  1. concentrationconcentrated in vacuo
  2. filtrationthe resulting precipitate was filtered off
  3. washrinsed with water
  4. dissolutionThe solid was dissolved in DCM
  5. washThe organic solution was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered off
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was purified by column chromatography [SiO2, 80 g, 20 min, EtOAc/heptane= 0/100 for 2 min

Sources & evidence

ORD record
ord-0bd9a62c9cb94c489a37f1087f9804a4
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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