N-ethyl-N-methylcarbamoyl chloride

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

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

Procedure: 250 mg (0.74 mmol) of 5-(4-ethylphenyl)-N-phenylpiperidine-3-carboxamide (Example 17A) and 117 mg (0.96 mmol, 1.3 eq.) of ethyl(methyl)carbamoyl chloride were reacted according to General Method 3. Yield: 215 mg (74% of theory)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Mix 7.9 g (0.02 mol) of (S)-1-(3-hydroxyphenyl)-N,N-dimethyl-N—((S)-1-phenylethyl)ethanaminium iodide (formula VIII) with 180 ml of acetonitrile, 1.7 g (0.03 mol) of potassium hydroxide, 3.6 (0.03 mol) ethyl(methyl)carbamic chloride and 0.1 g of macrogol 400 at room temperature, heat it to 60° C. and react it for 12 hours. After it is cooled to room temperature, filter it and reduce the pressure to recover the solvent and receive 10.2 g of red-brown liquid to be directly used in the next reaction. react it for 12 hours After it is cooled to room temperature filter it to recover the solvent to be directly used in the next reaction

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Mix 7.9 g (0.02 mol) of (S)-1-(3-hydroxyphenyl)-N,N-dimethyl-N—((S)-1-phenylethyl)ethanaminium iodide (formula VIII) with 100 ml of methanol, 4.1 g (0.03 mol) of potassium carbonate, 3.6 g (0.03 mol) ethyl(methyl)carbamic chloride and 0.1 g of macrogol 400 at room temperature, heat it to 60° C. and react it for 12 hours. After it is cooled to room temperature, filter it and reduce the pressure to recover the solvent and receive 9.0 g of red-brown liquid to be directly used in the next reaction. react it for 12 hours After it is cooled to room temperature filter it to recover the solvent to be directly used in the next reaction

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Mix 7.9 g (0.02 mol) of(S)-1-(3-hydroxyphenyl)-N,N-dimethyl-N—((S)-1-phenylethyl)ethanaminium iodide (formula VIII) with 180 ml of acetonitrile, 4.1 g (0.03 mol) of potassium carbonate, 3.6 (0.03 mol) ethyl(methyl)carbamic chloride and 0.1 g of tetrabutylammonium bromide at room temperature, heat it to 60° C. and react it for 12 hours. After it is cooled to room temperature, filter it and reduce the pressure to recover the solvent and receive 9.5 g of red-brown liquid to be directly used in the next reaction. react it for 12 hours After it is cooled to room temperature filter it to recover the solvent to be directly used in the next reaction

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

Procedure: Mix 7.9 g (0.02 mol) (S)-1-(3-hydroxyphenyl)-N,N-dimethyl-N—((S)-1-phenylethyl)ethanaminium iodide (formula VIII) with 180 ml of acetonitrile, 4.1 g (0.03 mol) of potassium carbonate, 3.6 g (0.03 mol) ethyl(methyl)carbamic chloride and 0.1 g of macrogol 400 at room temperature, let it react at 20° C. for 16 hours. Filter it and reduce the pressure to recover 9.8 g of red-brown liquid to be directly used in the next reaction. react at 20° C. for 16 hours Filter it to recover 9.8 g of red-brown liquid to be directly used in the next reaction

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Mix 7.9 g (0.02 mol) (S)-1-(3-hydroxyphenyl)-N,N-dimethyl-N—((S)-1-phenylethyl)ethanaminium iodide (formula VIII) with 180 ml of acetonitrile, 4.1 g (0.03 mol) of potassium carbonate, 3.6 g (0.03 mol) ethyl(methyl)carbamic chloride and 0.1 g of macrogol 400 at room temperature, heat the mixture to 60° C. and let it react for 12 hours. After cooling to room temperature, filter it and reduce the pressure to recover the solvent and receive 10.3 g of red-brown liquid to be directly used in the next reaction. react for 12 hours After cooling to room temperature filter it to recover the solvent to be directly used in the next reaction

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Mix 7.9 g (0.02 mol) (S)-1-(3-hydroxyphenyl)-N,N-dimethyl-N—((S)-1-phenylethyl)ethanaminium iodide (formula VIII) with 180 ml of acetonitrile, 4.1 g (0.03 mol) of potassium carbonate, 3.6 g (0.03 mol) ethyl(methyl)carbamic chloride and 0.1 g of macrogol 400 at room temperature, heat the mixture to 60° C. and let it react for 12 hours. After cooling to room temperature, filter it and reduce the pressure to recover the solvent and receive 10.3 g of red-brown liquid to be directly used in the next reaction. react for 12 hours After cooling to room temperature filter it to recover the solvent to be directly used in the next reaction

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

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

Procedure: Ethylmethyl carbamyl chloride (15.5 g, 127.57 mmol) was added to a stirred suspension of 6-hydroxy-1-indanone (17.2 g, 116.1 mmol) and potassium carbonate (31.8 g, 188 mmol) in acetonitrile (800 mL) at room temperature over a period of 15 minutes. The reaction mixture was heated to reflux and refluxed for 18 hours. The reaction mixture was cooled to ambient temperature, the solvent evaporated and the residue was diluted with water (250 mL) and extracted three times with toluene (250 mL). The combined organic phase was dried on MgSO4 and toluene was evaporated in a rotary evaporator. The crude crystalline product was purified by crystallization from 2-propanol (200 mL), collected by filtration, and dried under vacuum at 50° C. to afford the title compound (22 g, 81.5%). 1H NMR (300 MHz, CDCl3) δ ppm 7.47-7.44 (2H, m, Ar), 7.36 (1H, dd, J 8.4 and 2.1, Ar), 3.52-3.37 (2H, m, NCH2CH3), 3.14-3.108 [2H, m, OCCH2CH2 and incl. NCH3 (two rotamers), at 3.08 and 2.99 (3H, s, Me)], 2.74-2.71 (2H, m, OCCH2CH2) and 1.25 and 1.19 (two rotamers) (3H,two triplets, J 6.9). Mass Spectrum (FAB+) [MH+]=234 The reaction mixture was heated to reflux refluxed for 18 hours the solvent evaporated the residue was diluted with water (250 mL) extracted three times with toluene (250 mL) The combined organic phase was dried on MgSO4 and toluene was evaporated in a rotary evaporator The crude crystalline product was purified by crystallization from 2-propanol (200 mL) collected by filtration dried under vacuum at 50° C.

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

Procedure: Ethylmethyl carbamyl chloride (15.5 g, 127.57 mmol) was added to a stirred suspension of 6-hydroxy-1-indanone (17.2 g, 116.1 mmol) and potassium carbonate (31.8 g, 188 mmol) in acetonitrile (800 mL) at room temperature over a period of 15 minutes. The reaction mixture was heated to reflux and refluxed for 18 hours. The reaction mixture was cooled to ambient temperature, the solvent evaporated and the residue was diluted with water (250 mL) and extracted three times with toluene (250 mL). The combined organic phase was dried on MgSO4 and toluene was evaporated in a rotary evaporator. The crude crystalline product was purified by crystallization from 2-propanol (200 mL), collected by filtration, and dried under vacuum at 50° C. to afford the title compound (22 g, 81.5%). 1H NMR (300 MHz, CDCl3) δ ppm 7.47-7.44 (2H, m, Ar), 7.36 (1H, dd, J 8.4 and 2.1, Ar), 3.52-3.37 (2H, m, NCH2CH3), 3.14-3.108 [2H, m, OCCH2CH2 and incl. NCH3 (two rotamers), at 3.08 and 2.99 (3H, s, Me)], 2.74-2.71 (2H, m, OCCH2CH2) and 1.25 and 1.19 (two rotamers) (3H,two triplets, J 6.9). Mass Spectrum (FAB+) [MH+]=234 The reaction mixture was heated to reflux refluxed for 18 hours the solvent evaporated the residue was diluted with water (250 mL) extracted three times with toluene (250 mL) The combined organic phase was dried on MgSO4 and toluene was evaporated in a rotary evaporator The crude crystalline product was purified by crystallization from 2-propanol (200 mL) collected by filtration dried under vacuum at 50° C.

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

Procedure: Ethylmethyl carbamyl chloride (15.5 g, 127.57 mmol) was added to a stirred suspension of 6-hydroxy-1-indanone (17.2 g, 116.1 mmol) and potassium carbonate (31.8 g, 188 mmol) in acetonitrile (800 mL) at room temperature over a period of 15 minutes. The reaction mixture was heated to reflux and refluxed for 18 hours. The reaction mixture was cooled to ambient temperature, the solvent evaporated and the residue was diluted with water (250 mL) and extracted three times with toluene (250 mL). The combined organic phase was dried on MgSO4 and toluene was evaporated in a rotary evaporator. The crude crystalline product was purified by crystallization from 2-propanol (200 mL), collected by filtration, and dried under vacuum at 50° C. to afford the title compound (22 g, 81.5%). 1H NMR (300 MHz, CDCl3) δ ppm 7.47-7.44 (2H, m, Ar), 7.36 (1H, dd, J 8.4 and 2.1, Ar), 3.52-3.37 (2H, m, NCH2CH3), 3.14-3.108 [2H, m, OCCH2CH2 and incl. NCH3 (two rotamers), at 3.08 and 2.99 (3H, s, Me)], 2.74-2.71 (2H, m, OCCH2CH2) and 1.25 and 1.19 (two rotamers) (3H,two triplets, J 6.9). Mass Spectrum (FAB+) [MH+]=234 The reaction mixture was heated to reflux refluxed for 18 hours the solvent evaporated the residue was diluted with water (250 mL) extracted three times with toluene (250 mL) The combined organic phase was dried on MgSO4 and toluene was evaporated in a rotary evaporator The crude crystalline product was purified by crystallization from 2-propanol (200 mL) collected by filtration dried under vacuum at 50° C.