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

HRID 1362474Notes

Reaction equation

HRID 1362474 reaction equation
[F:1][C:2]1[C:3]([O:19][CH3:20])=[C:4]([C@H:8]([CH3:18])[CH2:9][C@:10]([OH:17])([C:13]([F:16])([F:15])[F:14])[CH:11]=O)[CH:5]=[CH:6][CH:7]=1.[NH2:21][C:22]1[CH:31]=[CH:30][C:29]([F:32])=[C:28]2[C:23]=1[CH:24]=[CH:25][C:26](=[O:33])[NH:27]2>C1(C)C(C)=CC=CC=1.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4]>[F:32][C:29]1[CH:30]=[CH:31][C:22]([N:21]=[CH:11][C@@:10]([OH:17])([C:13]([F:14])([F:15])[F:16])[CH2:9][C@H:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=2[O:19][CH3:20])[CH3:18])=[C:23]2[C:28]=1[NH:27][C:26](=[O:33])[CH:25]=[CH:24]2

Participants

5

Reactant 2

HCID 179891895-amino-8-fluoroquinolin-2(1H)-oneHCID 25180225(2R*,4R*)-4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentanal

Product 1

HCID 669693378-fluoro-5-{[(2R*,4R*)-4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentylidene]amino}quinolin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 7237O-XyleneSolvent

Procedure

In the same way as in Example 1, 300 mg (1.01 mmol) of (2R*,4R*)-4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentanal, 180 mg (1.01 mmol) of 5-amino-8-fluoroquinolone and 0.48 ml of titanium tetraisopropoxide in 9 ml of xylene are reacted to give 8-fluoro-5-{[(2R*,4R*)-4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentylidene]amino}quinolin-2(1H)-one. 80 mg of imine purified by column chromatography (silica gel, hexane; CH2Cl2/i-PrOH 0-5%) are cyclized, in the same way as in Example 1, at −40° C. using 1.7 ml (1.5 mmol) of 1 M boron tribromide solution to give the desired product and the ether-cleaved Example 8.

Sources & evidence

ORD record
ord-124d2f4424354005a45915ccac62e921
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

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