1-(2,8-Dichloroquinolin-3-yl)ethanol → 1-(2,8-Dichloroquinolin-3-yl)-ethanone
Reaction equation
[Cl:1][C:2]1[C:11]([CH:12]([OH:14])[CH3:13])=[CH:10][C:9]2[C:4](=[C:5]([Cl:15])[CH:6]=[CH:7][CH:8]=2)[N:3]=1>C1(C)C=CC=CC=1.O=[Mn]=O>[Cl:1][C:2]1[C:11]([C:12](=[O:14])[CH3:13])=[CH:10][C:9]2[C:4](=[C:5]([Cl:15])[CH:6]=[CH:7][CH:8]=2)[N:3]=1Participants
Reactant 1
Product 1
Reagents, catalysts & solvents 2
Procedure
A mixture of 1-(2,8-dichloroquinolin-3-yl)ethanol (5.0 g, 21 mmol) and MnO2 (18 g, 10 eq) in toluene (200 mL) were heated to reflux for 2 h. Filtration followed with removal of solvent gave a white solid as 1-(2,8-dichloroquinolin-3-yl)-ethanone (4.5 g, 91%). A solution of this solid (5.0 g, 21 mmol) in THF (50 mL) was added to a solution of (+)-DIP-Cl (14.7 g, 2.2 eq) in THF (150 mL) at −78° C. dropwise. The reaction was slowly warmed up to rt over night. The reaction was then quenched with acetone (23 mL) and stirred at 0° C. for 1 h before addition of EtOAc. The reaction was warmed up to rt and washed with 10% Na2CO3 and water. Chiral HPLC on IA column (isopropanol in hexane, 10%) showed a ratio of 19:1 for two enantiomers. The combined crude products were concentrated under high vacuum and purified by column chromatography on silica gel (EtOAc/hexane, 1/3) to give a white solid which is recrystallized from a mixture of EtOAc (30 mL) and Hexane (210 mL). A white needle was obtained. 1H NMR (400 MHz, CDCl3) δ ppm 8.43 (s, 1H), 7.84 (d, J=8.0 Hz, 1H), 7.79 (d, J=8.0 Hz, 1H), 7.50 (t, J=8.0 Hz, 1H), 5.40 (q, J=8.0 Hz, 1H), 1.63 (d, J=8.0 Hz, 3H). Mass Spectrum (ESI) m/e=242 (M+1).
Workup
- temperaturewere heated
- temperatureto reflux for 2 h
- filtrationFiltration
- customfollowed with removal of solvent
Sources & evidence
- ORD record
- ord-a49aef8653474f389153726f294a3002
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08901135B2
Reaction notes
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