4-[(4-methoxyphenyl)methyl]piperidine

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

Procedure: A solution of chloroacetamide 6 (41 mg; 0.118 mmol), piperidine 7.8 (27 mg; 0.132 mmol) and DIPEA (30 μL; 0.172 mmol) in 2.5 mL of 3:2 acetonitrile:THF was reacted at rt for 8 days; whereupon the reaction was concentrated on a rotary evaporator then purified on silica gel (20 mL) with 12:1 EtOAc:i-PrOH yielding a glassy material. A solution of the product in DCM plus hexanes was evaporated leaving a white solid (23 mg; 38%). LC (method B) tR=12.8 min; 1H NMR (200 MHz, CDCl3) δ 9.53 (brs, 1H), 8.37 (m, 2H), 7.48 (m, 3H), 7.22 (s, 1H), 7.08 (m, 2H), 6.84 (m, 3H), 6.62 (brs, 1H), 5.50 (brt, J=5.5 Hz, 1H), 3.79 (s, 3H), 3.68 (m, 2H), 3.53 (m, 2H), 3.10 (s, 2H), 2.88 (m, 2H), 2.54 (m, 2H), 2.20 (m, 2H), 1.85 (s, 3H), 1.80-1.20 (m, 5H); ESIMS 517.0 (28) [MH+], 259.1 (100). whereupon the reaction was concentrated on a rotary evaporator then purified on silica gel (20 mL) with 12:1 EtOAc A solution of the product in DCM plus hexanes was evaporated leaving a white solid (23 mg; 38%)

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

Procedure: 2.80 g (0.02 mol) of potassium carbonate are added to a solution of 5 g (0.02 mol) of 2-bromo-4'-chloropropiophenone and 4.15 g (0.02 mol) of 4-(4-methoxybenzyl)-piperidine in 60 ml of dry ethanol and the mixture is heated under reflux for 5 hours, with stirring, and then left to stand for 48 hours. It is left to cool and filtered, the filter cake being washed with alcohol, and the filtrate is evaporated. An orange oily residue remains, which is taken up in a mixture of water and diethyl ether. The organic phase is separated off and the aqueous phase is extracted a second time with diethyl ether. The organic phases are combined, dried and evaporated to give 7.45 g of an orange-yellow oily residue, which crystallises partially at ambient temperature and which is used as such in the subsequent reduction. the mixture is heated under reflux for 5 hours left It is left to cool filtered the filter cake being washed with alcohol the filtrate is evaporated which is taken up in a mixture of water and diethyl ether The organic phase is separated off the aqueous phase is extracted a second time with diethyl ether dried evaporated

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

Procedure: The title compound is prepared from N-(4-methanesulfonylamino-phenyl)-oxalamic acid and 4-(4-methoxy-benzyl)-piperidine according to the method described in Example 1c. Melting Point: 206-208° C. (diethylether)

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

Procedure: The title compound is prepared from N-(2-oxo-2,3-dihydro-benzoxazol-6-yl)-oxalamic acid (Example 43e) and 4-(4-methoxy-benzyl)-piperidine according to the method described in Example 1c. Melting Point: 193-197° C. (diisopropylether)

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

Procedure: The title compound is prepared from N-(2-oxo-2,3-dihydro-1H-indol-5-yl)-oxalamic acid (Example 101b) and 4-(4-methoxy-benzyl)-piperidine [U.S. Pat. No. 3,632,767 (1972)] according to the method described in Example 1c. Melting Point: 215-217° C. (diethylether)

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

Procedure: A solution of chloroacetamide 6 (41 mg; 0.118 mmol), piperidine 7.8 (27 mg; 0.132 mmol) and DIPEA (30 μL; 0.172 mmol) in 2.5 mL of 3:2 acetonitrile:THF was reacted at rt for 8 days; whereupon the reaction was concentrated on a rotary evaporator then purified on silica gel (20 mL) with 12:1 EtOAc:i-PrOH yielding a glassy material. A solution of the product in DCM plus hexanes was evaporated leaving a white solid (23 mg; 38%). LC (method B) tR=12.8 min; 1H NMR (200 MHz, CDCl3) δ 9.53 (brs, 1H), 8.37 (m, 2H), 7.48 (m, 3H), 7.22 (s, 1H), 7.08 (m, 2H), 6.84 (m, 3H), 6.62 (brs, 1H), 5.50 (brt, J=5.5 Hz, 1H), 3.79 (s, 3H), 3.68 (m, 2H), 3.53 (m, 2H), 3.10 (s, 2H), 2.88 (m, 2H), 2.54 (m, 2H), 2.20 (m, 2H), 1.85 (s, 3H), 1.80-1.20 (m, 5H); ESIMS 517.0 (28) [MH+], 259.1 (100). whereupon the reaction was concentrated on a rotary evaporator then purified on silica gel (20 mL) with 12:1 EtOAc A solution of the product in DCM plus hexanes was evaporated leaving a white solid (23 mg; 38%)