酮替芬杂质18

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Magnesium turnings (3.42 g, 143 mmol) were suspended in 15 mL of dry THF under nitrogen. To this was added CH2Br2 (1.25 mL, 14.5 mmol) and a vigorous reaction was observed. The reaction was heated to reflux, and 4-chloro-1-methyl-piperidine (21 mL, 128 mmol) was added. The reaction was refluxed for 1 h. The reaction was allowed to cool, and the supernatant was transferred via cannula to a stirring solution of compound 2c (8 g, 128 mmol) in THF at room temperature. The slurry was rinsed with 2×20 mL THF and the supernatant was transferred. At that time, all of the starting ketone had been consumed. To the reaction was added saturated sodium bicarbonate, and the mixture was extracted with ethyl acetate. The combined organics were dried over magnesium sulfate, filtered, and concentrated. The crude product Compound 1d was used without further purification. MS m/z (MH+) 388.14. a vigorous reaction The reaction was heated to reflux The reaction was refluxed for 1 h to cool The slurry was rinsed with 2×20 mL THF At that time, all of the starting ketone had been consumed To the reaction was added saturated sodium bicarbonate the mixture was extracted with ethyl acetate The combined organics were dried over magnesium sulfate filtered concentrated The crude product Compound 1d was used without further purification

反应条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of magnesium (1.8 g, 74 mmol) in dry THF (50 mL) in a flame-dried round bottomed flask under nitrogen was added 4-chloro-1-methylpiperidine (9.0 g, 68 mmol). A crystal of iodine and a catalytic amount of cyclohexylmagnesium chloride was added and the mixture was heated to reflux for 2 h. A gray precipitate formed, which was removed via vacuum filtration under a nitrogen atmosphere. To the filtrate was added a solution of 2-aminobenzonitrile (1.6 g, 14 mmol) in dry THF (15 mL). The stirred mixture was heated to 45° C. for 2 h. Ice was added and the reaction was quenched with 1 M sulfuric acid. The mixture was extracted with ethyl acetate and the acidic aqueous layer was then neutralized with 1 N sodium hydroxide, concentrated on a rotary evaporator and extracted with ethyl acetate. The combined organics were dried over sodium sulfate, filtered and concentrated to afford (2-aminophenyl)(1-methylpiperidin-4-yl)methanone as a yellow oil (1.0 g, 7%). the mixture was heated to reflux for 2 h A gray precipitate formed which was removed via vacuum filtration under a nitrogen atmosphere Ice was added the reaction was quenched with 1 M sulfuric acid The mixture was extracted with ethyl acetate concentrated on a rotary evaporator extracted with ethyl acetate The combined organics were dried over sodium sulfate filtered concentrated