Water → 2-(3-Bromo-phenyl)-6-fluoro-4-hydroxy-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester

HRID 1801083Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[N:11]=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=1.[CH:21](=[O:25])[CH:22]([CH3:24])[CH3:23].O>O1CCCC1.O.[O-]S(C(F)(F)F)(=O)=O.[Yb+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[C:6]2[C:5]=1[NH:11][CH:12]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=1)[C:22]([CH3:24])([CH3:23])[CH:21]2[OH:25])=[O:20]

Participants

Conditions

Temperature: 25 °C

Procedure

To a mixture of 2-{[1-(3-bromo-phenyl)-methylidene]-amino}-5-fluoro-benzoic acid methyl ester (50 g, 59.8 mmol) and ytterbium(III) triflate hydrate (3.7 g, 5.95 mmol) in dry tetrahydrofuran (30 mL) at 25° C. was added isobutyraldehyde (4.3 g, 59.5 mmol) and water (1.1 mL, 59.5 mmol) dropwise. The reaction mixture was stirred at 25° C. for 5 h. Then the reaction mixture was concentrated in vacuo and the residue was extracted with ethyl acetate (2×100 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to afford 2-(3-bromo-phenyl)-6-fluoro-4-hydroxy-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (24.3 g, 100%) as a light yellow oil: LC/MS m/e calcd for C19H19BrFNO3 M+: 408.3, observed: 408.1.

Workup

concentrationThen the reaction mixture was concentrated in vacuo
extractionthe residue was extracted with ethyl acetate (2×100 mL)
washwashed with brine
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-e20e1036798f43bea080208efcb91766
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08344137B2

Reaction notes

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