Sodium Methoxide → 3-fluoro-6-methoxy-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine
Reaction equation
[F:1][C:2]1[C:3]([NH:9][CH2:10][CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[N:4][C:5](F)=[CH:6][CH:7]=1.[CH3:17][O-:18].[Na+]>CO>[F:1][C:2]1[C:3]([NH:9][CH2:10][CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[N:4][C:5]([O:18][CH3:17])=[CH:6][CH:7]=1Participants
Procedure
To a solution of 3,6-difluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine (5 g, 21.91 mmol) in MeOH (35 mL) was added sodium methoxide (25 wt. % in MeOH, 15.03 mL, 65.7 mmol). The resulting mixture was heated in a steel bomb at about 135° C. for ˜18 hr. The mixture then was cooled to ambient temperature and concentrated in vacuo. The resulting residue was taken up in water (˜250 mL) yielding a precipitate, which was collected by filteration, and then washed with water. The solid then was dissolved in toluene (10 mL)/DCM (10 mL), decanted from the dark brownish film and concentrated in vacuo. The resulting residue was dried in high vacuo providing crude 3-fluoro-6-methoxy-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine as a nearly colorless oil, which was directly used in the next reaction without further purification. Yield: 4.96 g. LCMS (m/z): 241.1 [M+H]+; Retention time=0.87 min.
Workup
- concentrationconcentrated in vacuo
- customyielding a precipitate, which
- customwas collected by filteration
- washwashed with water
- dissolutionThe solid then was dissolved in toluene (10 mL)/DCM (10 mL)
- customdecanted from the dark brownish film
- concentrationconcentrated in vacuo
- customThe resulting residue was dried in high vacuo
Sources & evidence
- ORD record
- ord-4eac80cfe8ef40f584201bdcb40f5bd4
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08778951B2
Reaction notes
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