methyl 2-piperidin-4-ylacetate;hydrochloride

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirring suspension of piperidin-4-yl-acetic acid hydrochloride in MeOH (15 mL) at −5° C. was added thionyl chloride (1.12 mL, 15.3 mmol) dropwise. The reaction mixture was allowed to reach to RT then heated to 40° C. for 4 h. The reaction mixture was concentrated in vacuo and the resulting white solid was azeotroped with toluene twice. Washed with ether and filtered to give 2.7 g (quantitative yield). MS(ESI) 158.2 (M+H+). to reach to RT The reaction mixture was concentrated in vacuo the resulting white solid was azeotroped with toluene twice Washed with ether filtered to give 2.7 g (quantitative yield)

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 2.18 g of 1-(4-cyanophenyl)-4-iodomethyl-piperidine (mixture from Example XXV), 1.26 g of methyl-4-piperidyl-acetate-hydrochloride and 1.35 g of triethylamine in 150 ml of dimethylformamide is heated to 130° C. for 24 hours. After cooling, the solvent is removed under reduced pressure and the residue is chromatographed over silica gel with methylene chloride/methanol (30:1). The solvent is removed under reduced pressure and the crude product is used for the next stage of synthesis without any further purification. After cooling the solvent is removed under reduced pressure the residue is chromatographed over silica gel with methylene chloride/methanol (30:1) The solvent is removed under reduced pressure the crude product is used for the next stage of synthesis without any further purification

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

実験手順: 2.3 g of 4-carboxy-1-(5-cyanopyrid-2-yl)-piperidine, 2.0 g of methyl 4-piperidylacetate hydrochloride, 4.8 g of 2-[(1H)-benzotriazol-1-yl]-1,1,3,3-tetramethyl-uronium tetrafluoroborate and 5 ml of triethylamine in 75 ml of dimethylformamide is stirred at ambient temperature for 16 hours. The solvent is removed under reduced pressure. The residue is diluted with water and the aqueous phase is extracted with ethyl acetate. The organic phase is washed with water and saturated saline solution and dried over sodium sulphate. The solvent is removed under reduced pressure and the residue is chromatographed over silica gel. Yield: 2.75 g (74% of theory), Melting point: 112°-115° C. Rf value: 0.40 (silica gel; methylene chloride/methanol=15:1) The solvent is removed under reduced pressure The residue is diluted with water the aqueous phase is extracted with ethyl acetate The organic phase is washed with water and saturated saline solution dried over sodium sulphate The solvent is removed under reduced pressure the residue is chromatographed over silica gel

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

実験手順: A mixture of 2-Chloro-5-nitropyridine (1.59 g, 10 mmol) and methyl piperidin-4-ylacetate hydrochloride (1.8 g, 10 mmol) (prepared as described in Patent Application WO 2000029407) in DMA (50 mL) was treated with 2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine (BEMP) (15 g of a 2.2 mmol/g loading on polystyrene support, 33 mmol). The resulting mixture was stirred for 2.5 h then filtered through diatomaceous earth. Volatile material was removed by evaporation to give the title compound (740 mg, 21%) as a solid; 1H NMR δ 1.08-1.28 (2H, m), 1.77 (2H, d), 1.99-2.12 (1H, m), 2.29 (2H, d), 3.07 (2H, t), 3.60 (3H, s), 4.51 (2H, d), 6.94 (1H, d), 8.13-8.25 (1H, m), 8.95 (d, 1H); MS m/e MH+ 280. then filtered through diatomaceous earth Volatile material was removed by evaporation

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirring suspension of piperidin-4-yl-acetic acid hydrochloride in MeOH (15 mL) at −5° C. was added thionyl chloride (1.12 mL, 15.3 mmol) dropwise. The reaction mixture was allowed to reach to RT then heated to 40° C. for 4 h. The reaction mixture was concentrated in vacuo and the resulting white solid was azeotroped with toluene twice. Washed with ether and filtered to give 2.7 g (quantitative yield). MS(ESI) 158.2 (M+H+). to reach to RT The reaction mixture was concentrated in vacuo the resulting white solid was azeotroped with toluene twice Washed with ether filtered to give 2.7 g (quantitative yield)