Boron tribromide → 2-{4-Fluoro-alpha-[(2-methylquinazolin-5-yl)amino]-2-methoxybenzyl}-1,1,1-trifluoro-4-methylpent-3-en-2-ol
Reaction equation
B(Br)(Br)Br.[F:5][C:6]1[CH:34]=[CH:33][C:9]([CH:10]([C:23]([OH:32])([CH2:28][C:29]([CH3:31])=[CH2:30])[C:24]([F:27])([F:26])[F:25])[NH:11][C:12]2[CH:21]=[CH:20][CH:19]=[C:18]3[C:13]=2[CH:14]=[N:15][C:16]([CH3:22])=[N:17]3)=[C:8]([O:35][CH3:36])[CH:7]=1>CCCCCC.C(OCC)(=O)C>[F:5][C:6]1[CH:34]=[CH:33][C:9]([CH:10]([C:23]([OH:32])([CH:28]=[C:29]([CH3:30])[CH3:31])[C:24]([F:26])([F:25])[F:27])[NH:11][C:12]2[CH:21]=[CH:20][CH:19]=[C:18]3[C:13]=2[CH:14]=[N:15][C:16]([CH3:22])=[N:17]3)=[C:8]([O:35][CH3:36])[CH:7]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
Analogously to Example 6, 340 mg (1.1 mmol) of 4-(4-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanal and 211 mg (1.32 mmol) of 5-amino-2-methylquinazoline (described in Example 6) are reacted with 0.46 ml (2.2 mmol) of titanium tetraethylate to form imine. After analogous rearrangement with boron tribromide and subsequent chromatography on silica gel with hexane-ethyl acetate (0-50%), 156 mg of a mixture that consists of 2-{4-fluoro-alpha-[(2-methylquinazolin-5-yl)amino]-2-methoxybenzyl}-1,1,1-trifluoro-4-methylpent-4-en-2-ol and 2-{4-fluoro-alpha-[(2-methylquinazolin-5-yl)amino]-2-methoxybenzyl}-1,1,1-trifluoro-4-methylpent-3-en-2-ol is obtained. The separation is carried out by means of preparative thin-layer chromatography on silica gel (dichloromethane/2-propanol 5%) and yields 51 mg of the main component and 9 mg of the minor component.
Sources & evidence
- ORD record
- ord-9090185b097c419c8f39212f897e2578
- Source dataset
- uspto-grants-2008_10
- Patent number
- US07442794B2
Reaction notes
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