Methylamine → 5-benzyloxy-2-difluoromethyl-1-methyl-1H-pyridin-4-one
Reaction equation
[CH3:1][NH2:2].[CH2:3]([O:10][C:11]1[C:12](=[O:20])[CH:13]=[C:14]([CH:17]([F:19])[F:18])O[CH:16]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.ClCCl>CO.CCOCC>[CH2:3]([O:10][C:11]1[C:12](=[O:20])[CH:13]=[C:14]([CH:17]([F:19])[F:18])[N:2]([CH3:1])[CH:16]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1Participants
Procedure
A 2.0M methylamine solution in methanol (19.0 mL, 38.0 mmol) was added to a suspension of 5-benzyloxy-2-difluoromethyl-pyran-4-one (3.15 g, 12.5 mmol) in methanol (18 mL). The reaction mixture slowly turned into a clear yellow solution. The progress of the reaction was monitored by TLC using a mixture of methanol and dichloromethane (1/20, v/v) as eluant, and HPLC method 1 as described above. After 70 minutes, the reaction mixture was concentrated in vacuo to obtain an oil. The oil was diluted with ether and allowed to stir overnight at room temperature. A precipitate had formed and it was collected by filtration. The solid was washed with ether, and the title compound was obtained as an off white solid (2.50 g, 75% yield). The purity of this material was analysed by HPLC Method 1 (peak area percent is 98.8% at λ=288 nm) as described above. 1H NMR (400 MHz, DMSO-D6) δ (ppm): 7.75 (s, 1H), 7.44-7.34 (m, 5H, ArH), 7.12 (t, J=53.0 Hz, 1H, CF2H), 6.48 (s, 1H), 5.02 (s, 2H, OCH2), 3.71 (s, 3H, N—CH3).
Workup
- concentrationthe reaction mixture was concentrated in vacuo
- customto obtain an oil
- customA precipitate had formed
- filtrationit was collected by filtration
- washThe solid was washed with ether
Sources & evidence
- ORD record
- ord-4007f623761b44e7886ff9d508c660a9
- Source dataset
- uspto-grants-2011_09
- Patent number
- US08026261B2
Reaction notes
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