乙基 4-羟基哌啶-4-羧酸乙酯

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To an ice-cold solution of ethyl 4-hydroxypiperidine-4-carboxylate (0.60 g, 3.44 mmol) in EtOH (15 mL) was added DIPEA (2.95 mL, 17.24 mmol) followed by the addition of 5-bromo-2-chloropyrimidine (0.67 g, 3.44 mmol). The reaction was heated to 80° C. for 3 h then cooled to rt, water added and extracted with EtOAc (3×100 mL). The combined organics were washed with brine, dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified over 100-200 M silica-gel using 20% EtOAc:hexane to obtain the desired product as a yellow solid (0.57 g, 88%). 1H NMR (DMSO-d6): δ 8.44 (s, 2H), 5.58 (s, 1H), 4.27 (m, 2H), 4.10 (q, J=7.20 Hz, 2H), 3.28 (m, 2H), 1.81 (m, 2H), 1.66 (m, 2H), and 1.18 (t, J=7.20 Hz, 3H). then cooled to rt extracted with EtOAc (3×100 mL) The combined organics were washed with brine dried over anhydrous Na2SO4 filtered evaporated under reduced pressure The crude residue was purified over 100-200 M silica-gel

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To an ice-cold solution of ethyl 4-hydroxypiperidine-4-carboxylate (0.60 g, 3.44 mmol) in EtOH (15 mL) was added DIPEA (2.95 mL, 17.24 mmol) followed by the addition of 5-bromo-2-chloropyrimidine (0.67 g, 3.44 mmol). The reaction was heated to 80° C. for 3 h then cooled to rt, water added and extracted with EtOAc (3×100 mL). The combined organics were washed with brine, dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified over 100-200 M silica-gel using 20% EtOAc:hexane to obtain the desired product as a yellow solid (0.57 g, 88%). 1H NMR (DMSO-d6): δ 8.44 (s, 2H), 5.58 (s, 1H), 4.27 (m, 2H), 4.10 (q, J=7.20 Hz, 2H), 3.28 (m, 2H), 1.81 (m, 2H), 1.66 (m, 2H), and 1.18 (t, J=7.20 Hz, 3H). then cooled to rt extracted with EtOAc (3×100 mL) The combined organics were washed with brine dried over anhydrous Na2SO4 filtered evaporated under reduced pressure The crude residue was purified over 100-200 M silica-gel

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-hydroxypiperidine-4-carboxylic acid (1.20 g, 8.26 mmol) in EtOH (30 ml) was added conc. HCl (5 ml) at rt and the mixture heated up to 80° C. for 2-3 h. After completion (by TLC), solvent was evaporated under reduced pressure to obtain the desired product (1.20 g, crude) which was carried forward for next step without further purification. 1H NMR (D2O): δ 4.20 (q, J=7.20 Hz, 2H), 3.28 (M, 4H), 2.22 (m, 2H), 1.91 (m, 2H), and 1.22 (t, J=7.20 Hz, 3H). After completion (by TLC), solvent was evaporated under reduced pressure

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

实验步骤: The 4-hydroxypiperidine-4-carboxylic acid (118 mg) obtained in the step (a) of Example 68 was dissolved in 1 N hydrochloric acid/ethanol (5 ml) solution, and the resulting solution was stirred at room temperature for 17 hours and then under reflux for 6 hours. The reaction mixture was concentrated to obtain crude ethyl 4-hydroxypiperidine-4-carboxylate. This crude ethyl 4-hydroxypiperidine-4-carboxylate was used in the following reaction without purification. under reflux for 6 hours The reaction mixture was concentrated

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

实验步骤: The 4-hydroxypiperidine-4-carboxylic acid (118 mg) obtained in the step (a) of Example 68 was dissolved in 1 N hydrochloric acid/ethanol (5 ml) solution, and the resulting solution was stirred at room temperature for 17 hours and then under reflux for 6 hours. The reaction mixture was concentrated to obtain crude ethyl 4-hydroxypiperidine-4-carboxylate. This crude ethyl 4-hydroxypiperidine-4-carboxylate was used in the following reaction without purification. under reflux for 6 hours The reaction mixture was concentrated

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To an ice-cold solution of ethyl 4-hydroxypiperidine-4-carboxylate (0.60 g, 3.44 mmol) in EtOH (15 mL) was added DIPEA (2.95 mL, 17.24 mmol) followed by the addition of 5-bromo-2-chloropyrimidine (0.67 g, 3.44 mmol). The reaction was heated to 80° C. for 3 h then cooled to rt, water added and extracted with EtOAc (3×100 mL). The combined organics were washed with brine, dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified over 100-200 M silica-gel using 20% EtOAc:hexane to obtain the desired product as a yellow solid (0.57 g, 88%). 1H NMR (DMSO-d6): δ 8.44 (s, 2H), 5.58 (s, 1H), 4.27 (m, 2H), 4.10 (q, J=7.20 Hz, 2H), 3.28 (m, 2H), 1.81 (m, 2H), 1.66 (m, 2H), and 1.18 (t, J=7.20 Hz, 3H). then cooled to rt extracted with EtOAc (3×100 mL) The combined organics were washed with brine dried over anhydrous Na2SO4 filtered evaporated under reduced pressure The crude residue was purified over 100-200 M silica-gel

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-hydroxypiperidine-4-carboxylic acid (1.20 g, 8.26 mmol) in EtOH (30 ml) was added conc. HCl (5 ml) at rt and the mixture heated up to 80° C. for 2-3 h. After completion (by TLC), solvent was evaporated under reduced pressure to obtain the desired product (1.20 g, crude) which was carried forward for next step without further purification. 1H NMR (D2O): δ 4.20 (q, J=7.20 Hz, 2H), 3.28 (M, 4H), 2.22 (m, 2H), 1.91 (m, 2H), and 1.22 (t, J=7.20 Hz, 3H). After completion (by TLC), solvent was evaporated under reduced pressure