2-(4-fluorophenyl)-1-piperidin-1-ylethanone

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A well stirred mixture of 111.8 g of piperidine, 103 g of pyridine and one liter of anhydrous ether was treated dropwise with 220 g of freshly distilled 4-fluorophenyl acetyl chloride. This mixture was stirred overnight, then filtered and the filtrate washed successively with water twice, 0.1N sodium hydroxide twice, 0.1N hydrochloric acid twice, water and saturated sodium chloride, then dried in vacuo. The residue was distilled giving a yellow liquid which crystallized on standing, giving 245 g of N-(4-fluorophenylacetyl)piperidine. This mixture was stirred overnight filtered the filtrate washed successively with water twice 0.1N sodium hydroxide twice, 0.1N hydrochloric acid twice, water and saturated sodium chloride, then dried in vacuo The residue was distilled giving a yellow liquid which crystallized

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Fluorophenylacetic acid (280 g, 1.82 mol) was suspended in 1.9 L toluene followed by the careful addition of 185 mL thionyl chloride (303 g, 2.545 mol). The reaction was heated to 105° C. for 16 hr (overnight). The reaction was allowed to cool to room temperature and the volatiles were removed in vacuo. The crude acid chloride was dissolved in 1.9 L THF, cooled to 0° C., and 0.72 L piperidine (618 g, 7.27 mol) was added. The reaction vessel was allowed to warm to ambient temperature for 18 hr. The mixture was quenched with a saturated solution of aq. NaHCO3 and extracted several times with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, and filtered on a fritted funnel. The volatiles were removed in vacuo and the crude residue was purified on silica gel and eluted with a mixture of EtOAc/heptanes (0-75% gradient elution). This furnished the title compound. 1H-NMR (CDCl3): δ 1.32-1.42 (m, 2H), 1.48-1.64 (m, 4H), 3.34-3.42 (m, 2H), 3.54-3.60 (m, 2H), 3.69 (s, 2H), 6.90-7.05 (m, 2H), 7.18-7.24 (m, 2H) ppm. to cool to room temperature the volatiles were removed in vacuo The crude acid chloride was dissolved in 1.9 L THF cooled to 0° C. to warm to ambient temperature for 18 hr The mixture was quenched with a saturated solution of aq. NaHCO3 extracted several times with EtOAc The combined organic extracts were washed with brine dried over Na2SO4 filtered on a fritted funnel The volatiles were removed in vacuo the crude residue was purified on silica gel eluted with a mixture of EtOAc/heptanes (0-75% gradient elution)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A well stirred mixture of 111.8 g of piperidine, 103 g of pyridine and one liter of anhydrous ether was treated dropwise with 220 g of freshly distilled 4-fluorophenyl acetyl chloride. This mixture was stirred overnight, then filtered and the filtrate washed successively with water twice, 0.1N sodium hydroxide twice, 0.1N hydrochloric acid twice, water and saturated sodium chloride, then dried in vacuo. The residue was distilled giving a yellow liquid which crystallized on standing, giving 245 g of N-(4-fluorophenylacetyl)piperidine. This mixture was stirred overnight filtered the filtrate washed successively with water twice 0.1N sodium hydroxide twice, 0.1N hydrochloric acid twice, water and saturated sodium chloride, then dried in vacuo The residue was distilled giving a yellow liquid which crystallized