4-Methylquinoline → HCID 11339121, compound

Participants

Reaction Conditions

Reaction Steps

To a chilled (−78° C.) solution of 105.2 μL (0.79 mmol) of lepidine in 5 mL of THF at −78° C. was added 398 μL (0.79 mmol) of a 2 M solution of lithium diisopropyl amide in THF/ethyl benzene/heptane. The reaction was then warmed to −30° C. After 30 minutes, the mixture was cooled to −78° C. and then 200 mg (0.724 mmol) of 1,1,1-trifluoro-3-(6-fluoro-4-methylchroman-4-yl)propan-2-one (Example 1) in 1 μL of THF was added. The reaction mixture was warmed to room temperature for 1 hour and monitored by TLC. The reaction mixture was then cooled to −78° C., quenched with saturated ammonium chloride solution, warmed to room temperature, and THF was removed by concentrating in vacuo. The residue was extracted with diethyl ether, dried over sodium sulfate, and concentrated. The residue was purified on PLC plate (hexanes-EtOAc (6:4)) to afford a mixture of two diastereomers. The diastereomers were partially purified by a second PLC plate (CH2Cl2-MeOH (95:5)). One of the diastereomers was triturated with diethyl ether and the solid was collected by filtration to afford 20 mg (6%) of the title compound as a single diastereomer (M+1=420). The other diastereomer was chromatographed a second time on a PLC plate (CH2Cl2-MeOH (95:5)). The solids were triturated with diethyl ether and collected by filtration to afford 10 mg (3%) of the second diastereomer (M+1=420).

Provenance & Evidence