Allylamine → 1-Allyl-5-benzyloxy-2-difluoromethyl-1H-pyridin-4-one
Reaction equation
[CH2:1]([O:8][C:9]1[C:10](=[O:18])[CH:11]=[C:12]([CH:15]([F:17])[F:16])O[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:19]([NH2:22])[CH:20]=[CH2:21]>CO>[CH2:19]([N:22]1[CH:14]=[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:10](=[O:18])[CH:11]=[C:12]1[CH:15]([F:16])[F:17])[CH:20]=[CH2:21]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
A mixture of 5-benzyloxy-2-difluoromethyl-pyran-4-one (4.00 g, 15.8 mmol), allylamine (3.60 mL, 47.5 mmol) in methanol (40 mL) was stirred at room temperature for 1 hour. The reaction mixture was evaporated to dryness, and the residual solid was dissolved in 10 mL of ethyl acetate, and again concentrated in vacuo. The solid was suspended in a mixture of ethyl acetate and ether, then collected by suction filtration and thoroughly washed with ether. The off-white solid was dried to constant weight in a vacuum oven at 40° C. to afford the title product (3.38 g, 73% yield). HPLC purity (peak area percent) is 98.9% at λ=278 nm using HPLC Method 1 as described above. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.35-7.43 (m, 5H, ArH), 7.16 (s, 1H), 6.79 (s, 1H), 6.48 (t, J=53.1 Hz, 1H, CF2H), 5.80-5.86 (m, 1H), 5.29 (d, J=10.4 Hz, 1H), 5.22 (s, 2H, OCH2), 5.10 (d, J=17.1 Hz, 1H), 4.58 (d, J=5.2 Hz, 2H); MS-ESI (m/z): 291.9 [M+1]+, 91.0.
Workup
- customThe reaction mixture was evaporated to dryness
- dissolutionthe residual solid was dissolved in 10 mL of ethyl acetate
- concentrationagain concentrated in vacuo
- additionThe solid was suspended in a mixture of ethyl acetate and ether
- filtrationcollected by suction filtration
- washthoroughly washed with ether
- customThe off-white solid was dried to constant weight in a vacuum oven at 40° C.
Sources & evidence
- ORD record
- ord-9445276cb0df4130811dde9c3ab9a4eb
- Source dataset
- uspto-grants-2011_09
- Patent number
- US08026261B2
Reaction notes
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