methyl 4-hydroxypiperidine-2-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of compound 12 (7 g, 1 eq.) and Pd/C (1.4 g, 20 w %) in dry ethanol (110 mL) was stirred overnight at room temperature under hydrogen. The mixture was filtered, and the filtrate was evaporated to give compound 31 as a yellow oil in quantitative yield. 1H NMR (CDCl3, 400 MHz) δ (ppm) 1.34-1.48 (m, 2H), 1.84 (s, 2H), 1.90-1.96 (m, 1H), 2.27-2.33 (m, 1H), 2.60-2.67 (m, 1H), 3.21 (dt, J=3.86 and 12.79 Hz, 1H), 3.38 (dd, J=3.08 and 10.91 Hz, 1H), 3.70-3.78 (m, 1H), 3.75 (s, 3H). The mixture was filtered the filtrate was evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of compound 12 (7 g, 1 eq.) and Pd/C (1.4 g, 20 w %) in dry ethanol (110 mL) was stirred overnight at room temperature under hydrogen. The mixture was filtered, and the filtrate was evaporated to give compound 31 as a yellow oil in quantitative yield. 1H NMR (CDCl3, 400 MHz) δ (ppm) 1.34-1.48 (m, 2H), 1.84 (s, 2H), 1.90-1.96 (m, 1H), 2.27-2.33 (m, 1H), 2.60-2.67 (m, 1H), 3.21 (dt, J=3.86 and 12.79 Hz, 1H), 3.38 (dd, J=3.08 and 10.91 Hz, 1H), 3.70-3.78 (m, 1H), 3.75 (s, 3H). The mixture was filtered the filtrate was evaporated

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cold (5° C.) solution of methyl 4-hydroxypiperidine-2-carboxylate, 13a, (5.17 g, 32.48 mmol) and triethylamine (6.00 mL, 43.05 mmol) in CH2Cl2 (135 mL) was added dropwise benzyl chloroformate (6.20 mL, 43.43 mmol) over 10 min. The resulting solution was stirred at 5° C. for 1 hour and then allowed to warm to room temperature. The reaction mixture was diluted with water and the layers were separated. The aqueous was re-extracted with CH2Cl2 and the combined organics were dried over MgSO4, filtered and evaporated to dryness. The crude was passed through a plug of silica gel, eluting with 30-80% EtOAc/Hexanes to afford the desired product, 13b. to warm to room temperature the layers were separated The aqueous was re-extracted with CH2Cl2 the combined organics were dried over MgSO4 filtered evaporated to dryness eluting with 30-80% EtOAc/Hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of the product of step B (600 mg, 2.4 mmol) in methanol (15 mL) was added 10% palladium on carbon (60 mg) and ammonium formate (1.26 g, 20.0 mmol). The reaction mixture was heated to reflux for 2 h, cooled to ambient temperature then filtered through Celite. The filtrate was concentrated in vacuo to afford methyl 4-hydroxypiperidine-2-carboxylate (470 mg, 95%) as a colorless oil which was carried forward without purification: 1H NMR (CDCl3, 400 MHz) δ 3.76-3.74 (m, 4H), 3.44-3.41 (m, 1H), 3.26-3.21 (m, 1H), 2.70-2.63 (m, 1H), 2.33-2.28 (m 1H), 1.91-1.90 (m, 1H), 1.50-1.40 (m, 2H). The reaction mixture was heated to reflux for 2 h then filtered through Celite The filtrate was concentrated in vacuo

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cold (5° C.) solution of methyl 4-hydroxypiperidine-2-carboxylate, 13a, (5.17 g, 32.48 mmol) and triethylamine (6.00 mL, 43.05 mmol) in CH2Cl2 (135 mL) was added dropwise benzyl chloroformate (6.20 mL, 43.43 mmol) over 10 min. The resulting solution was stirred at 5° C. for 1 hour and then allowed to warm to room temperature. The reaction mixture was diluted with water and the layers were separated. The aqueous was re-extracted with CH2Cl2 and the combined organics were dried over MgSO4, filtered and evaporated to dryness. The crude was passed through a plug of silica gel, eluting with 30-80% EtOAc/Hexanes to afford the desired product, 13b. to warm to room temperature the layers were separated The aqueous was re-extracted with CH2Cl2 the combined organics were dried over MgSO4 filtered evaporated to dryness eluting with 30-80% EtOAc/Hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of compound 12 (7 g, 1 eq.) and Pd/C (1.4 g, 20 w %) in dry ethanol (110 mL) was stirred overnight at room temperature under hydrogen. The mixture was filtered, and the filtrate was evaporated to give compound 31 as a yellow oil in quantitative yield. 1H NMR (CDCl3, 400 MHz) δ (ppm) 1.34-1.48 (m, 2H), 1.84 (s, 2H), 1.90-1.96 (m, 1H), 2.27-2.33 (m, 1H), 2.60-2.67 (m, 1H), 3.21 (dt, J=3.86 and 12.79 Hz, 1H), 3.38 (dd, J=3.08 and 10.91 Hz, 1H), 3.70-3.78 (m, 1H), 3.75 (s, 3H). The mixture was filtered the filtrate was evaporated

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cold (5° C.) solution of methyl 4-hydroxypiperidine-2-carboxylate, 13a, (5.17 g, 32.48 mmol) and triethylamine (6.00 mL, 43.05 mmol) in CH2Cl2 (135 mL) was added dropwise benzyl chloroformate (6.20 mL, 43.43 mmol) over 10 min. The resulting solution was stirred at 5° C. for 1 hour and then allowed to warm to room temperature. The reaction mixture was diluted with water and the layers were separated. The aqueous was re-extracted with CH2Cl2 and the combined organics were dried over MgSO4, filtered and evaporated to dryness. The crude was passed through a plug of silica gel, eluting with 30-80% EtOAc/Hexanes to afford the desired product, 13b. to warm to room temperature the layers were separated The aqueous was re-extracted with CH2Cl2 the combined organics were dried over MgSO4 filtered evaporated to dryness eluting with 30-80% EtOAc/Hexanes