甲基 4-哌啶-4-基丁酸甲酯

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: To a suspension of 2 (1.96 g, 8.86 mmol), K2CO3 (2.82 g, 17.72 mmol) and acetone (100 mL) was added 2-(4-iodobutyl)-3a,7a-dihydroisoindole-1,3-dione (2.93 g, 8.86 mmol). The newly formed suspension was stirred at ambient temperature for 48 hours. The solid was vacuum filtered and the filtrate was concentrated under vacuum. The resulting residue was subjected to column chromatography eluting with 0-100% ethyl acetate in hexanes to afford the desired product 3 (0.63 g, 40%) as a white solid: 1H NMR (500 MHz; CDCl3) δ 1.16-1.28 (m, 3H), 1.65 (m, 2H), 1.60-1.72 (m, 4H), 1.86 (m, 2H), 2.26 (t, 2H), 2.32 (t, 2H), 2.88 (d, 2H) 3.64 (s, 3H), 3.70 (t, 2H), 7.68 (d, 2H), 7.72 (d, 2H). filtered the filtrate was concentrated under vacuum eluting with 0-100% ethyl acetate in hexanes

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

实验步骤: To a suspension of 2 (1.96 g, 8.86 mmol), K2CO3 (2.82 g, 17.72 mmol) and acetone (100 mL) was added 2-(4-iodobutyl)-3a,7a-dihydroisoindole-1,3-dione (2.93 g, 8.86 mmol). The newly formed suspension was stirred at ambient temperature for 48 hours. The solid was vacuum filtered and the filtrate was concentrated under vacuum. The resulting residue was subjected to column chromatography eluting with 0-100% ethyl acetate in hexanes to afford the desired product 3 (0.63 g, 40%) as a white solid: 1H NMR (500 MHz; CDCl3) δ 1.16-1.28 (m, 3H), 1.65 (m, 2H), 1.60-1.72 (m, 4H), 1.86 (m, 2H), 2.26 (t, 2H), 2.32 (t, 2H), 2.88 (d, 2H) 3.64 (s, 3H), 3.70 (t, 2H), 7.68 (d, 2H), 7.72 (d, 2H). filtered the filtrate was concentrated under vacuum eluting with 0-100% ethyl acetate in hexanes

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

实验步骤: Trimethylsilyl chloride (9.2 ml, 72.46 mmol) was added to a solution of 4-piperidin-4-yl-butyric acid (1) (5.00 g, 24.15 mmol) dissolved in anhydrous methanol (100 mL). The resulting solution was stirred at room temperature for 48 hours, and concentrated under vacuum to complete dryness to give 2 (4.50 g, 97%) as a white solid, which was used directly in the next step without further purification: 1H NMR (300 MHz, CD3OD) δ 1.20-1.46 (m, 4H), 1.52-1.74 (m, 3H), 1.96 (d, 2H), 2.35 (t, 2H), 2.96 (t, 2H), 3.36 (t, 2H), 3.68 (s, 3H); ESI MS m/z 186 [C10H19NO2+H]+. concentrated under vacuum

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: Following the same procedure described for the preparation of compound 3a, the compound 3b was synthesized in 40% yield from compound 2 as a yellow oil. 1H NMR (300 MHz, CD3OD) δ 1.21 (m, 4H), 1.42 (m, 1H), 1.49 (m, 2H), 1.83 (d, 2H), 1.93 (m, 2H), 2.31 (m, 2H), 2.69 (m, 2H), 2.99 (m, 2H), 3.35 (m, 2H), 3.60 (m, 5H), 4.50 (m, 2H), 7.28 (m, 5H). m/z (ESI): 334 [C20H31NO3+H]+.

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

实验步骤: Following the same procedure described for the preparation of compound 3a, the compound 3b was synthesized in 40% yield from compound 2 as a yellow oil. 1H NMR (300 MHz, CD3OD) δ 1.21 (m, 4H), 1.42 (m, 1H), 1.49 (m, 2H), 1.83 (d, 2H), 1.93 (m, 2H), 2.31 (m, 2H), 2.69 (m, 2H), 2.99 (m, 2H), 3.35 (m, 2H), 3.60 (m, 5H), 4.50 (m, 2H), 7.28 (m, 5H). m/z (ESI): 334 [C20H31NO3+H]+.

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

实验步骤: A solution of 2 (2.00 g, 10.8 mmol), (2-bromoethoxymethyl)benzene (2.31 g, 10.8 mmol), and triethylamine (4.5 ml, 32.4 mmol) in dichloromethane (30 mL) was stirred at room temperature overnight. Solvent was evaporated and the residue was purified by Flash™ chromatography (BIOTAGE, Inc) (9.3:0.7 dichloromethane/methanol, v/v) to provide 3a (1.3 g, 42%) as a yellow oil. 1H NMR (300 MHz, CD3OD) δ 1.30 (m, 5H), 1.66 (m, 2H), 1.87 (d, 2H), 2.37 (m, 2H), 2.58 (m, 2H), 3.04 (m, 2H), 3.39 (m, 2H), 3.65 (s, 3H), 3.80 (m, 2H), 4.55 (s, 2H), 7.37 (m, 5H). m/z (ESI): 320 [C19H29NO3+H]+. Solvent was evaporated the residue was purified by Flash™ chromatography (BIOTAGE, Inc) (9.3:0.7 dichloromethane/methanol, v/v)

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

实验步骤: A solution of 2 (2.00 g, 10.8 mmol), (2-bromoethoxymethyl)benzene (2.31 g, 10.8 mmol), and triethylamine (4.5 ml, 32.4 mmol) in dichloromethane (30 mL) was stirred at room temperature overnight. Solvent was evaporated and the residue was purified by Flash™ chromatography (BIOTAGE, Inc) (9.3:0.7 dichloromethane/methanol, v/v) to provide 3a (1.3 g, 42%) as a yellow oil. 1H NMR (300 MHz, CD3OD) δ 1.30 (m, 5H), 1.66 (m, 2H), 1.87 (d, 2H), 2.37 (m, 2H), 2.58 (m, 2H), 3.04 (m, 2H), 3.39 (m, 2H), 3.65 (s, 3H), 3.80 (m, 2H), 4.55 (s, 2H), 7.37 (m, 5H). m/z (ESI): 320 [C19H29NO3+H]+. Solvent was evaporated the residue was purified by Flash™ chromatography (BIOTAGE, Inc) (9.3:0.7 dichloromethane/methanol, v/v)

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

实验步骤: A solution of 2 (2.00 g, 10.8 mmol), (2-bromoethoxymethyl)benzene (2.31 g, 10.8 mmol), and triethylamine (4.5 ml, 32.4 mmol) in dichloromethane (30 mL) was stirred at room temperature overnight. Solvent was evaporated and the residue was purified by Flash™ chromatography (BIOTAGE, Inc) (9.3:0.7 dichloromethane/methanol, v/v) to provide 3a (1.3 g, 42%) as a yellow oil. 1H NMR (300 MHz, CD3OD) δ 1.30 (m, 5H), 1.66 (m, 2H), 1.87 (d, 2H), 2.37 (m, 2H), 2.58 (m, 2H), 3.04 (m, 2H), 3.39 (m, 2H), 3.65 (s, 3H), 3.80 (m, 2H), 4.55 (s, 2H), 7.37 (m, 5H). m/z (ESI): 320 [C19H29NO3+H]+. Solvent was evaporated the residue was purified by Flash™ chromatography (BIOTAGE, Inc) (9.3:0.7 dichloromethane/methanol, v/v)

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

实验步骤: To a suspension of 2 (1.96 g, 8.86 mmol), K2CO3 (2.82 g, 17.72 mmol) and acetone (100 mL) was added 2-(4-iodobutyl)-3a,7a-dihydroisoindole-1,3-dione (2.93 g, 8.86 mmol). The newly formed suspension was stirred at ambient temperature for 48 hours. The solid was vacuum filtered and the filtrate was concentrated under vacuum. The resulting residue was subjected to column chromatography eluting with 0-100% ethyl acetate in hexanes to afford the desired product 3 (0.63 g, 40%) as a white solid: 1H NMR (500 MHz; CDCl3) δ 1.16-1.28 (m, 3H), 1.65 (m, 2H), 1.60-1.72 (m, 4H), 1.86 (m, 2H), 2.26 (t, 2H), 2.32 (t, 2H), 2.88 (d, 2H) 3.64 (s, 3H), 3.70 (t, 2H), 7.68 (d, 2H), 7.72 (d, 2H). filtered the filtrate was concentrated under vacuum eluting with 0-100% ethyl acetate in hexanes