4-BENZYL-4-HYDROXYPIPERIDINE

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

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

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

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

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

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: To a solution of 4-benzyl-4-hydroxypiperidine (0.95 g, 5.0 mmol) and triethylamine (0.51 g, 5.0 mmol) in dichloromethane (10 mL) was added (R)-1-(4-methanesulfonyloxy-pyrimidin-2-yl)-ethyl butyrate (prepared according to the method of Preparation Eight, 123 g, 4.0 mmol) and stirred at ambient temperature for 18 h. The mixture was washed once with water, once with saturated aqueous sodium chloride and the organic layer was dried over sodium sulfate and filtered. The filtrate was evaporated to an oil which was purified by flash chromatography (95:5 dichloromethane:methanol) to give the title compound of Example 174, Step A as a viscous oil, 0.99 g (52%). 1H NMR (CDCl3, 300 MHz) δ 0.95 (t, 3H), 1.53 (d, 3H), 1.65-1.78 (m, 4H), 1.88 (m, 2H), 2.08 (m, 2H), 2.48 (t, 2H), 3.45 (m, 2H), 4.42 (br s, 1H), 5.68 (q, 1H), 6.41 (d, 1H), 7.30-7.48 (m, 5H), 8.18 (d, 1H); MS (CI) 384 (MH+). prepared according to the method of Preparation Eight, 123 g, 4.0 mmol) and The mixture was washed once with water, once with saturated aqueous sodium chloride the organic layer was dried over sodium sulfate filtered The filtrate was evaporated to an oil which was purified by flash chromatography (95:5 dichloromethane:methanol)

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

Procedure: A mixture of 1-mesyl-4-(3-methylphenyl)but-3-yne (344 mg, 1.45 mmol), 4-benzyl-4-hydroxy-piperidine (332 mg, 1.73 mmol) and K2CO3 (598 mg, 4.34 mmol) in 15 mL of CH3CN is refluxed for 12 hr. The mixture is filtered and washed with EtOAc (3×20 mL). The filtrate is evaporated in vacuo and is purified by flash chromatography to give the product as a brown oil (100 mg, 20%) 1H NMR (CDCl3) 1.37 (s, 1 H) , 1.55 (m, 2 H) 1.75 (m, 2 H), 2.30 (s, 3 H), 2.41 (m, 2 H), 2.60 (m, 3 H), 2.75 (m, 5 H), 7.11-7.31 (m, 9 H) is refluxed for 12 hr The mixture is filtered washed with EtOAc (3×20 mL) The filtrate is evaporated in vacuo is purified by flash chromatography

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

Procedure: A mixture of 1-mesyl-4-phenylbut-3-yne (300 mg, 1.34 mmol), 4-benzyl-4-hydroxypiperidine (307 mg, 1.61 mmol) and K2CO3 (555 mg, 4.02 mmol) in 15 mL of CH3CN is refluxed for 12 hr. The mixture is filtered and washed with EtOAc (3×20 mL). The filtrate is evaporated in vacuo and is purified by flash chromatography to give the product as an off-white solid (130 mg, 30%): mp 80-82° C.; 1H NMR (CDCl3) 1.50 (m, 3 H), 1.74 (m, 2 H), 2.41 (m, 2 H), 2.58 (m, 3 H), 2.75 (m, 5 H), 7.11-7.38 (m, 10 H). is refluxed for 12 hr The mixture is filtered washed with EtOAc (3×20 mL) The filtrate is evaporated in vacuo is purified by flash chromatography

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

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