tert-butyl 4-(iodomethyl)piperidine-1-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A mixture of 1-(t-butoxycarbonyl)piperidin-4-yl methanesulfonate (13.58 g, 46.4 mmol) and sodium iodide (34.68 g, 232 mmol) in acetone (80 mL) was heated to reflux for 3 h. The mixture was partitioned between ether (350 mL) and water (350 mL). The organic layer was washed with saturated aq. brine (250 mL), and the aqueous layers were extracted in succession with ether (250 mL). The combined organic layers were dried (sodium sulfate), decanted, and evaporated to give the title compound (14.8 g) as a pale yellow oil. was heated to reflux for 3 h The mixture was partitioned between ether (350 mL) and water (350 mL) The organic layer was washed with saturated aq. brine (250 mL) the aqueous layers were extracted in succession with ether (250 mL) The combined organic layers were dried (sodium sulfate) decanted evaporated

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

Procedure: A mixture of 1-(t-butoxycarbonyl)piperidin-4-yl methanesulfonate (13.58 g, 46.4 mmol) and sodium iodide (34.68 g, 232 mmol) in acetone (80 mL) was heated to reflux for 3 h. The mixture was partitioned between ether (350 mL) and water (350 mL). The organic layer was washed with saturated aq. brine (250 mL), and the aqueous layers were extracted in succession with ether (250 mL). The combined organic layers were dried (sodium sulfate), decanted, and evaporated to give the title compound (14.8 g) as a pale yellow oil. was heated to reflux for 3 h The mixture was partitioned between ether (350 mL) and water (350 mL) The organic layer was washed with saturated aq. brine (250 mL) the aqueous layers were extracted in succession with ether (250 mL) The combined organic layers were dried (sodium sulfate) decanted evaporated

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

Procedure: A mixture of 1-(t-butoxycarbonyl)piperidin-4-yl methanesulfonate (13.58 g, 46.4 mmol) and sodium iodide (34.68 g, 232 mmol) in acetone (80 mL) was heated to reflux for 3 h. The mixture was partitioned between ether (350 mL) and water (350 mL). The organic layer was washed with saturated aq. brine (250 mL), and the aqueous layers were extracted in succession with ether (250 mL). The combined organic layers were dried (sodium sulfate), decanted, and evaporated to give the title compound (14.8 g) as a pale yellow oil. was heated to reflux for 3 h The mixture was partitioned between ether (350 mL) and water (350 mL) The organic layer was washed with saturated aq. brine (250 mL) the aqueous layers were extracted in succession with ether (250 mL) The combined organic layers were dried (sodium sulfate) decanted evaporated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-isopropyl-5-methyl-2-oxo-N-(piperidin-4-ylmethyl)-1,2-dihydroquinoline-3-carboxamide (300 mg, 0.88 mmol, step 4 in preparation 3) in N,N-dimethylformamide (30 mL), tert-butyl 4-(iodomethyl)piperidine-1-caroxylate (343 mg, 1.05 mmol, Villalobos Anabella et al., J. Med. Chem., 1994, 37, 2721) and potassium carbonate (610 mg, 4.4 mmol) were added at room temperature. The mixture was heated at 80° C. overnight. After cooled to room temperature, water (30 mL) was added and extracted with diethyl ether (50 mL×2). The combined organic layer was washed with water (20 mL×2), brine (20 mL), dried over magnesium sulfate and concentrated in vacuo gave yellow oil, which was chromatographed on a column of silica gel eluting with ethyl 25% ammonium oxide/methanol/dichloromethane (3:30:1000) to give 154 mg (32%) of the title compound as a clear colorless oil. After cooled to room temperature extracted with diethyl ether (50 mL×2) The combined organic layer was washed with water (20 mL×2), brine (20 mL) dried over magnesium sulfate concentrated in vacuo gave yellow oil, which was chromatographed on a column of silica gel eluting with ethyl 25% ammonium oxide/methanol/dichloromethane (3:30:1000)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-isopropyl-5-methyl-2-oxo-N-(piperidin-4-ylmethyl)-1,2-dihydroquinoline-3-carboxamide (300 mg, 0.88 mmol, step 4 in preparation 3) in N,N-dimethylformamide (30 mL), tert-butyl 4-(iodomethyl)piperidine-1-caroxylate (343 mg, 1.05 mmol, Villalobos Anabella et al., J. Med. Chem., 1994, 37, 2721) and potassium carbonate (610 mg, 4.4 mmol) were added at room temperature. The mixture was heated at 80° C. overnight. After cooled to room temperature, water (30 mL) was added and extracted with diethyl ether (50 mL×2). The combined organic layer was washed with water (20 mL×2), brine (20 mL), dried over magnesium sulfate and concentrated in vacuo gave yellow oil, which was chromatographed on a column of silica gel eluting with ethyl 25% ammonium oxide/methanol/dichloromethane (3:30:1000) to give 154 mg (32%) of the title compound as a clear colorless oil. After cooled to room temperature extracted with diethyl ether (50 mL×2) The combined organic layer was washed with water (20 mL×2), brine (20 mL) dried over magnesium sulfate concentrated in vacuo gave yellow oil, which was chromatographed on a column of silica gel eluting with ethyl 25% ammonium oxide/methanol/dichloromethane (3:30:1000)

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

Procedure: A mixture of 1-(t-butoxycarbonyl)piperidin-4-yl methanesulfonate (13.58 g, 46.4 mmol) and sodium iodide (34.68 g, 232 mmol) in acetone (80 mL) was heated to reflux for 3 h. The mixture was partitioned between ether (350 mL) and water (350 mL). The organic layer was washed with saturated aq. brine (250 mL), and the aqueous layers were extracted in succession with ether (250 mL). The combined organic layers were dried (sodium sulfate), decanted, and evaporated to give the title compound (14.8 g) as a pale yellow oil. was heated to reflux for 3 h The mixture was partitioned between ether (350 mL) and water (350 mL) The organic layer was washed with saturated aq. brine (250 mL) the aqueous layers were extracted in succession with ether (250 mL) The combined organic layers were dried (sodium sulfate) decanted evaporated

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

Procedure: A mixture of 1-(t-butoxycarbonyl)piperidin-4-yl methanesulfonate (13.58 g, 46.4 mmol) and sodium iodide (34.68 g, 232 mmol) in acetone (80 mL) was heated to reflux for 3 h. The mixture was partitioned between ether (350 mL) and water (350 mL). The organic layer was washed with saturated aq. brine (250 mL), and the aqueous layers were extracted in succession with ether (250 mL). The combined organic layers were dried (sodium sulfate), decanted, and evaporated to give the title compound (14.8 g) as a pale yellow oil. was heated to reflux for 3 h The mixture was partitioned between ether (350 mL) and water (350 mL) The organic layer was washed with saturated aq. brine (250 mL) the aqueous layers were extracted in succession with ether (250 mL) The combined organic layers were dried (sodium sulfate) decanted evaporated

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

Procedure: A mixture of 1-(t-butoxycarbonyl)piperidin-4-yl methanesulfonate (13.58 g, 46.4 mmol) and sodium iodide (34.68 g, 232 mmol) in acetone (80 mL) was heated to reflux for 3 h. The mixture was partitioned between ether (350 mL) and water (350 mL). The organic layer was washed with saturated aq. brine (250 mL), and the aqueous layers were extracted in succession with ether (250 mL). The combined organic layers were dried (sodium sulfate), decanted, and evaporated to give the title compound (14.8 g) as a pale yellow oil. was heated to reflux for 3 h The mixture was partitioned between ether (350 mL) and water (350 mL) The organic layer was washed with saturated aq. brine (250 mL) the aqueous layers were extracted in succession with ether (250 mL) The combined organic layers were dried (sodium sulfate) decanted evaporated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The procedure described in Example 7a was followed using 1-methyl isoquinoline (0.50 g, 3.49 mmol), 1M LDA (4.2 mL, 4.2 mmol), and 4-iodomethyl-1-piperidinecarboxylic acid, 1-(1,1-dimethylethyl) ester (1.2 g, 3.84 mmol) in dry THF (45 mL) except that after addition of the reagents, the mixture was stirred at −78° C. for 1.75 hours. Purification by chromatography (30% EtOAc/toluene) gave the title compound (0.784 g, 66%) as a yellow oil. after addition of the reagents Purification by chromatography (30% EtOAc/toluene)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The procedure described in Example 7a was followed using 1-methyl isoquinoline (0.50 g, 3.49 mmol), 1M LDA (4.2 mL, 4.2 mmol), and 4-iodomethyl-1-piperidinecarboxylic acid, 1-(1,1-dimethylethyl) ester (1.2 g, 3.84 mmol) in dry THF (45 mL) except that after addition of the reagents, the mixture was stirred at −78° C. for 1.75 hours. Purification by chromatography (30% EtOAc/toluene) gave the title compound (0.784 g, 66%) as a yellow oil. after addition of the reagents Purification by chromatography (30% EtOAc/toluene)