5-amino-8-fluoroquinolin-2(1H)-one → 5-{[(2R,4R)-4-(3-chloro-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}-8-fluoroquinolin-2(1H)-one

HRID 1362543Notes

Reaction equation

HRID 1362543 reaction equation
[Cl:1][C:2]1[C:3]([O:21][CH3:22])=[C:4]([C@H:9]([CH2:19][CH3:20])[CH2:10][C@:11]([OH:18])([C:14]([F:17])([F:16])[F:15])[CH:12]=O)[CH:5]=[CH:6][C:7]=1[F:8].[NH2:23][C:24]1[CH:33]=[CH:32][C:31]([F:34])=[C:30]2[C:25]=1[CH:26]=[CH:27][C:28](=[O:35])[NH:29]2>CC(C)([O-])C.[Ti+4].CC(C)([O-])C.CC(C)([O-])C.CC(C)([O-])C>[Cl:1][C:2]1[C:3]([O:21][CH3:22])=[C:4]([C@H:9]([CH2:19][CH3:20])[CH2:10][C@:11]([OH:18])([C:14]([F:16])([F:15])[F:17])[CH:12]=[N:23][C:24]2[CH:33]=[CH:32][C:31]([F:34])=[C:30]3[C:25]=2[CH:26]=[CH:27][C:28](=[O:35])[NH:29]3)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

4

Reactant 2

HCID 179891895-amino-8-fluoroquinolin-2(1H)-oneHCID 86615335(2R,4R)-4-(3-chloro-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal

Product 1

HCID 866153385-{[(2R,4R)-4-(3-chloro-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}-8-fluoroquinolin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 6451515Titanum tetra t-butoxideCatalyst

Procedure

In the same way as in Example 148, 300 mg (0.88 mmol) of (2R,4R)-4-(3-chloro-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal, 156 mg (0.88 mmol) of 5-amino-8-fluoroquinolin-2(1H)-one and 0.55 ml of titanium tert-butoxide is reacted to give 5-{[(2R,4R)-4-(3-chloro-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}-8-fluoroquinolin-2(1H)-one. 480 mg of crude imine are cyclized in the same way as in Example 148 at −30° C. with 7.6 ml (7.6 mmol) of 1 M boron tribromide solution to give the desired product. Column chromatography on silica gel (hexane/ethyl acetate 0-70%) yields 119 mg of desired product.

Sources & evidence

ORD record
ord-dbc60bf704e04288be28d6c3d8c50306
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

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