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Boron tribromide → 2-{4-Fluoro-alpha-[(2-methylquinazolin-5-yl)amino]-2-methoxybenzyl}-1,1,1-trifluoro-4-methylpent-3-en-2-ol

HRID 2118078
Notes
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Reaction equation

HRID 2118078 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]=1
ParticipantsProcedureSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 179850612-{4-Fluoro-alpha-[(2-methylquinazolin-5-yl)amino]-2-methoxybenzyl}-1,1,1-trifluoro-4-methylpent-4-en-2-ol

Product 1

HCID 179850632-{4-Fluoro-alpha-[(2-methylquinazolin-5-yl)amino]-2-methoxybenzyl}-1,1,1-trifluoro-4-methylpent-3-en-2-ol

Reagents, catalysts & solvents 1

HCID 21226206Ethyl acetate hexaneSolvent

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
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07442794B2

Reaction notes

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