P-Chloroacetophenone → Methyl {1-[1-(4-chlorophenyl)ethyl]azetidin-3-ylidene}(3,5-difluorophenyl)acetate
Reaction equation
[NH:1]1[CH2:4][C:3](=[C:5]([C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=2)[C:6]([O:8][CH3:9])=[O:7])[CH2:2]1.[CH3:18][C:19]([C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=1)=O.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([CH:19]([N:1]2[CH2:4][C:3](=[C:5]([C:10]3[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=3)[C:6]([O:8][CH3:9])=[O:7])[CH2:2]2)[CH3:18])=[CH:22][CH:23]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of 0.142 g (0.5 mmole) of methyl azetidin-3-ylidene(3,5-difluorophenyl)acetate, 0.142 g (1 mmol) of 4-chloroacetophenone and 0.15 mL (12 mmol) of triethylamine in 5 mL of dichloroethane was stirred at room temperature. After 5 min, 0.422 g (2 mmol) of sodium triacetoxyborohydride was added and the mixture was stirred at room temperature for 3 h. The reaction was quenched by addition of saturated KHCO3 solution and the mixture was partitioned between 10 mL ether and 2 mL saturated KHCO3 solution. The layers were separated and the organic layer was dried over Na2SO4, and concentrated. The residue was purified by reverse phase chromatography (Waters Xterra C18, 19 mm×10 mm) using a gradient of CH3CN—H2O-Et3N (20:80:0.1 to 60:40:0.1) to afford the title compound; Mass Spectrum: m/e=378 (M+1 35Cl) and 380 (M+1 35Cl).
Workup
- customThe reaction was quenched by addition of saturated KHCO3 solution
- customthe mixture was partitioned between 10 mL ether and 2 mL saturated KHCO3 solution
- customThe layers were separated
- dry with materialthe organic layer was dried over Na2SO4
- concentrationconcentrated
- customThe residue was purified by reverse phase chromatography (Waters Xterra C18, 19 mm×10 mm)
Sources & evidence
- ORD record
- ord-0de440b1db484c91a738633f6dce88c8
- Source dataset
- uspto-grants-2011_03
- Patent number
- US07906503B2
Reaction notes
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