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

HRID 1801138Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([N:10]=[CH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([Br:18])[CH:13]=2)=[C:6]([Cl:19])[CH:5]=1.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.[CH:47](=[O:51])[CH:48]([CH3:50])[CH3:49].O>O1CCCC1>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[C:8]2[C:7](=[C:6]([Cl:19])[CH:5]=1)[NH:10][CH:11]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Br:18])[CH:13]=1)[C:48]([CH3:50])([CH3:49])[CH:47]2[OH:51])=[O:20]

Participants

Conditions

Temperature: 25 °C

Procedure

To a stirred mixture solution of 4-[(3-bromo-benzylidene)-amino]-3-chloro-benzoic acid methyl ester (39.8 g, 113.2 mmol) and ytterbium(III) triflate hydrate (10.5 g, 16.9 mmol) in dry tetrahydrofuran (100 mL) at 25° C. was added isobutyraldehyde (10.4 mL, 113.2 mmol) and water (2.1 mL, 113.2 mmol) dropwise. The reaction mixture was stirred at 25° C. for 16 h. Then the reaction mixture was concentrated in vacuo and the residue was extracted with ethyl acetate (2×200 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to afford 2-(3-bromo-phenyl)-8-chloro-4-hydroxy-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester (48 g, quant.) as a light yellow oil which was used for next step without further purification: LC/MS m/e calcd for C19H19BrClNO3 (M+H)+: 425.73, observed: 405.9 & 407.9.

Workup

concentrationThen the reaction mixture was concentrated in vacuo
extractionthe residue was extracted with ethyl acetate (2×200 mL)
washwashed with brine
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-aa3325369a474bc0898de9807764ae8d
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08344137B2

Reaction notes

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