Water → 2-(5-Bromo-pyridin-3-yl)-4-hydroxy-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester

HRID 1800965Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:20])[C:5]1[CH:10]=[CH:9][C:8]([N:11]=[CH:12][C:13]2[CH:14]=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=2)=[CH:7][CH:6]=1)[CH3:2].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>[CH2:1]([O:3][C:4]([C:5]1[CH:10]=[C:9]2[C:8](=[CH:7][CH:6]=1)[NH:11][CH:12]([C:13]1[CH:14]=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=1)[C:48]([CH3:50])([CH3:49])[CH:47]2[OH:51])=[O:20])[CH3:2]

Participants

Conditions

Temperature: 25 °C

Procedure

To a mixture of 4-[(5-bromo-pyridin-3-ylmethylene)-amino]-benzoic acid ethyl ester (16.3 g, 49 mmol) and ytterbium(III) triflate hydrate (3.1 g, 49 mmol) in dry tetrahydrofuran (100 mL) at 25° C. was added isobutyraldehyde (4.98 mL, 55 mmol) and water (0.89 mL, 49 mmol) dropwise. The reaction mixture was stirred at 25° C. for 12 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-(5-bromo-pyridin-3-yl)-4-hydroxy-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (16 g, 80%) as a light yellow oil which was used for next step without further purification: LC/MS m/e calcd for C19H21BrN2O3 (M+H)+: 406.29, observed: 405.1.

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-8066815b972e4b99ace929fbcc6dd01f
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08344137B2

Reaction notes

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