3-(2-oxopiperidin-1-yl)propanal

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

実験手順: A solution of ethyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate (0.79 g, 2.9 mmol) and 3-(2-oxo-1-piperidinyl)propanal (0.56 g, 3.6 mmol) under nitrogen in glacial acetic acid (10 mL) was treated with sodium triacetoxyborohydride (1.21 g, 5.7 mmol) at 0° C. for 30 min. After stirring for an additional 30 min., an additional 0.23 g of 3-(2-oxo-1-piperidinyl)propanal and 0.36 g sodium triacetoxyborohydride were added. After stirring another 1 h, an additional 0.145 g of 3-(2-oxo-1-piperidinyl)propanal and 0.3 g sodium triacetoxyborohydride were added and stirred at 0° C. for another ½ hour. The reaction was evaporated in vacuo and the residue was dissolved in CH2Cl2, washed with 2N Na2CO3, and back extracted the aqueous 2× with CH2Cl2. The organics were combined, washed with brine, dried over MgSO4, filtered and evaporated in vacuo. The residue was dissolved in CH2Cl2 and chromatographed on silica gel eluting with 10-100% acetone in hexanes to provide, after combining pure fractions and concentrating them in vacuo, the product as a clear viscous oil. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.25-1.31 (m, 3 H), 1.63-1.77 (m, 6 H), 2.19 (t, J=5.90 Hz, 2 H), 3.12-3.25 (m, 4 H), 3.24-3.39 (m, 2 H), 3.94 (s, 2 H), 4.26 (q, J=7.11 Hz, 2 H), 7.08-7.16 (m, 3 H), 7.31 (ddd, J=12.00, 5.33, 3.02 Hz, 2 H), 7.61 (t, J=5.69 Hz, 1 H), 7.76 (d, J=1.82 Hz, 1 H); ES+ MS: 414 (M+H+). After stirring another 1 h stirred at 0° C. for another ½ hour The reaction was evaporated in vacuo the residue was dissolved in CH2Cl2 washed with 2N Na2CO3 back extracted the aqueous 2× with CH2Cl2 washed with brine dried over MgSO4 filtered evaporated in vacuo The residue was dissolved in CH2Cl2 chromatographed on silica gel eluting with 10-100% acetone in hexanes to provide concentrating them in vacuo

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

実験手順: A solution of ethyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate (0.79 g, 2.9 mmol) and 3-(2-oxo-1-piperidinyl)propanal (0.56 g, 3.6 mmol) under nitrogen in glacial acetic acid (10 mL) was treated with sodium triacetoxyborohydride (1.21 g, 5.7 mmol) at 0° C. for 30 min. After stirring for an additional 30 min., an additional 0.23 g of 3-(2-oxo-1-piperidinyl)propanal and 0.36 g sodium triacetoxyborohydride were added. After stirring another 1 h, an additional 0.145 g of 3-(2-oxo-1-piperidinyl)propanal and 0.3 g sodium triacetoxyborohydride were added and stirred at 0° C. for another ½ hour. The reaction was evaporated in vacuo and the residue was dissolved in CH2Cl2, washed with 2N Na2CO3, and back extracted the aqueous 2× with CH2Cl2. The organics were combined, washed with brine, dried over MgSO4, filtered and evaporated in vacuo. The residue was dissolved in CH2Cl2 and chromatographed on silica gel eluting with 10-100% acetone in hexanes to provide, after combining pure fractions and concentrating them in vacuo, the product as a clear viscous oil. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.25-1.31 (m, 3 H), 1.63-1.77 (m, 6 H), 2.19 (t, J=5.90 Hz, 2 H), 3.12-3.25 (m, 4 H), 3.24-3.39 (m, 2 H), 3.94 (s, 2 H), 4.26 (q, J=7.11 Hz, 2 H), 7.08-7.16 (m, 3 H), 7.31 (ddd, J=12.00, 5.33, 3.02 Hz, 2 H), 7.61 (t, J=5.69 Hz, 1 H), 7.76 (d, J=1.82 Hz, 1 H); ES+ MS: 414 (M+H+). After stirring another 1 h stirred at 0° C. for another ½ hour The reaction was evaporated in vacuo the residue was dissolved in CH2Cl2 washed with 2N Na2CO3 back extracted the aqueous 2× with CH2Cl2 washed with brine dried over MgSO4 filtered evaporated in vacuo The residue was dissolved in CH2Cl2 chromatographed on silica gel eluting with 10-100% acetone in hexanes to provide concentrating them in vacuo

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

実験手順: A solution of 1-[3,3-bis(ethyloxy)propyl]-2-piperidinone (1.52 g, 6.61 mmol) in CH2Cl2 (100 mL) under nitrogen was treated with trifluoroacetic acid (TFA) (1.5 mL, 19.5 mmol) and stirred at ambient temperature for 1 h. After adding an additional 1.5 mL of TFA and monitoring by TLC (EtOAc, KMnO4 stain) for complete consumption of starting materials the reaction mixture was partitioned between CH2Cl2 and 1:1 Sat. NaHCO3:water (150 mL) solution. Extracted the aqueous with CH2Cl2 two additional times before combining the organics, washing them with brine, drying over MgSO4, filtering, and concentrating in vacuo to provide the desired product as a clear oil: 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.78-1.91 (m, 4 H), 2.67 (t, J=6.11 Hz, 2 H), 2.85 (td, J=6.42, 0.91 Hz, 2 H), 3.50 (t, J=5.48 Hz, 2 H), 3.71 (t, J=6.32 Hz, 2 H), 9.53-9.58 (m, 1 H); ES+ MS: 156 (M+H+). for complete consumption of starting materials the reaction mixture was partitioned between CH2Cl2 and 1:1 Sat. NaHCO3 Extracted the aqueous with CH2Cl2 two additional times washing them with brine drying over MgSO4 filtering concentrating in vacuo

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

実験手順: A solution of 1-[3,3-bis(ethyloxy)propyl]-2-piperidinone (1.52 g, 6.61 mmol) in CH2Cl2 (100 mL) under nitrogen was treated with trifluoroacetic acid (TFA) (1.5 mL, 19.5 mmol) and stirred at ambient temperature for 1 h. After adding an additional 1.5 mL of TFA and monitoring by TLC (EtOAc, KMnO4 stain) for complete consumption of starting materials the reaction mixture was partitioned between CH2Cl2 and 1:1 Sat. NaHCO3:water (150 mL) solution. Extracted the aqueous with CH2Cl2 two additional times before combining the organics, washing them with brine, drying over MgSO4, filtering, and concentrating in vacuo to provide the desired product as a clear oil: 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.78-1.91 (m, 4 H), 2.67 (t, J=6.11 Hz, 2 H), 2.85 (td, J=6.42, 0.91 Hz, 2 H), 3.50 (t, J=5.48 Hz, 2 H), 3.71 (t, J=6.32 Hz, 2 H), 9.53-9.58 (m, 1 H); ES+ MS: 156 (M+H+). for complete consumption of starting materials the reaction mixture was partitioned between CH2Cl2 and 1:1 Sat. NaHCO3 Extracted the aqueous with CH2Cl2 two additional times washing them with brine drying over MgSO4 filtering concentrating in vacuo

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

実験手順: A solution of 1-[3,3-bis(ethyloxy)propyl]-2-piperidinone (1.52 g, 6.61 mmol) in CH2Cl2 (100 mL) under nitrogen was treated with trifluoroacetic acid (TFA) (1.5 mL, 19.5 mmol) and stirred at ambient temperature for 1 h. After adding an additional 1.5 mL of TFA and monitoring by TLC (EtOAc, KMnO4 stain) for complete consumption of starting materials the reaction mixture was partitioned between CH2Cl2 and 1:1 Sat. NaHCO3:water (150 mL) solution. Extracted the aqueous with CH2Cl2 two additional times before combining the organics, washing them with brine, drying over MgSO4, filtering, and concentrating in vacuo to provide the desired product as a clear oil: 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.78-1.91 (m, 4 H), 2.67 (t, J=6.11 Hz, 2 H), 2.85 (td, J=6.42, 0.91 Hz, 2 H), 3.50 (t, J=5.48 Hz, 2 H), 3.71 (t, J=6.32 Hz, 2 H), 9.53-9.58 (m, 1 H); ES+ MS: 156 (M+H+). for complete consumption of starting materials the reaction mixture was partitioned between CH2Cl2 and 1:1 Sat. NaHCO3 Extracted the aqueous with CH2Cl2 two additional times washing them with brine drying over MgSO4 filtering concentrating in vacuo