N-(4-bromophenyl)prop-2-enamide

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

Procedure: N-(4-Bromo-phenyl)-acrylamide (0.3 g, 1.33 mmol) was dissolved in ethanol. Pyrrolidine (0.12 ml, 1.46 mmol) was added and the mixture was heated to reflux overnight. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate. Aqueous ammonium chloride was added and the aqueous layer was extracted twice with ethyl acetate. The organics were combined, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to yield the desired product. Yield 0.24 g, 60%. LCMS method: 2, RT: 2.67 min; MI: 297-299 [M+1]. the mixture was heated to reflux overnight The solvent was removed under reduced pressure the residue was dissolved in ethyl acetate Aqueous ammonium chloride was added the aqueous layer was extracted twice with ethyl acetate dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

Procedure: N-(4-Bromo-phenyl)-acrylamide (0.3 g, 1.33 mmol) was dissolved in ethanol. Pyrrolidine (0.12 ml, 1.46 mmol) was added and the mixture was heated to reflux overnight. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate. Aqueous ammonium chloride was added and the aqueous layer was extracted twice with ethyl acetate. The organics were combined, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to yield the desired product. Yield 0.24 g, 60%. LCMS method: 2, RT: 2.67 min; MI: 297-299 [M+1]. the mixture was heated to reflux overnight The solvent was removed under reduced pressure the residue was dissolved in ethyl acetate Aqueous ammonium chloride was added the aqueous layer was extracted twice with ethyl acetate dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

Procedure: This material was synthesized by the reaction of N-(4-bromophenyl)acrylamide with 4-(3-benzyloxyphenyl)-4-fluoro-3-methylpiperidine hydrochloride as described in Step 1 of Example 20. The desired compound was obtained as a light yellow solid in 65% yield.

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

Procedure: To a solution of N-(4-bromophenyl)acrylamide (340 mg, 1.50 mmol) in methanol (10 mL) was added 4-(3-benzyloxyphenyl)-4-fluoropiperidine hydrochloride (321 mg, 1.00 mmol) followed by sodium bicarbonate (840 mg, 10.0 mmol) and the resulting suspension stirred at room temperature for 52 hours. After this time the reaction was filtered and the filtrate concentrated under reduced pressure. The residue was treated with ethyl acetate (10 mL) and the resulting suspension re-filtered and concentrated under reduced pressure. The resulting solid was treated with 10% hydrogen chloride in methanol (10 mL) and the solution re-concentrated. Subsequent trituration with ethyl acetate (10 mL) afforded 3-[4-(3-benzyloxyphenyl)-4-fluoropiperidin-1-yl]-N-(4-bromophenyl)propionamide hydrochloride in 64% yield as a light yellow solid. After this time the reaction was filtered the filtrate concentrated under reduced pressure The residue was treated with ethyl acetate (10 mL) the resulting suspension re-filtered concentrated under reduced pressure The resulting solid was treated with 10% hydrogen chloride in methanol (10 mL) the solution re-concentrated

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

Procedure: To a solution of N-(4-bromophenyl)acrylamide (340 mg, 1.50 mmol) in methanol (10 mL) was added 4-(3-benzyloxyphenyl)-4-fluoropiperidine hydrochloride (321 mg, 1.00 mmol) followed by sodium bicarbonate (840 mg, 10.0 mmol) and the resulting suspension stirred at room temperature for 52 hours. After this time the reaction was filtered and the filtrate concentrated under reduced pressure. The residue was treated with ethyl acetate (10 mL) and the resulting suspension re-filtered and concentrated under reduced pressure. The resulting solid was treated with 10% hydrogen chloride in methanol (10 mL) and the solution re-concentrated. Subsequent trituration with ethyl acetate (10 mL) afforded 3-[4-(3-benzyloxyphenyl)-4-fluoropiperidin-1-yl]-N-(4-bromophenyl)propionamide hydrochloride in 64% yield as a light yellow solid. After this time the reaction was filtered the filtrate concentrated under reduced pressure The residue was treated with ethyl acetate (10 mL) the resulting suspension re-filtered concentrated under reduced pressure The resulting solid was treated with 10% hydrogen chloride in methanol (10 mL) the solution re-concentrated

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

Procedure: N-(4-Bromo-phenyl)-acrylamide (0.3 g, 1.33 mmol) was dissolved in ethanol. Pyrrolidine (0.12 ml, 1.46 mmol) was added and the mixture was heated to reflux overnight. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate. Aqueous ammonium chloride was added and the aqueous layer was extracted twice with ethyl acetate. The organics were combined, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to yield the desired product. Yield 0.24 g, 60%. LCMS method: 2, RT: 2.67 min; MI: 297-299 [M+1]. the mixture was heated to reflux overnight The solvent was removed under reduced pressure the residue was dissolved in ethyl acetate Aqueous ammonium chloride was added the aqueous layer was extracted twice with ethyl acetate dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

Procedure: N-(4-Bromo-phenyl)-acrylamide (0.3 g, 1.33 mmol) was dissolved in ethanol. Pyrrolidine (0.12 ml, 1.46 mmol) was added and the mixture was heated to reflux overnight. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate. Aqueous ammonium chloride was added and the aqueous layer was extracted twice with ethyl acetate. The organics were combined, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to yield the desired product. Yield 0.24 g, 60%. LCMS method: 2, RT: 2.67 min; MI: 297-299 [M+1]. the mixture was heated to reflux overnight The solvent was removed under reduced pressure the residue was dissolved in ethyl acetate Aqueous ammonium chloride was added the aqueous layer was extracted twice with ethyl acetate dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

Procedure: N-(4-Bromo-phenyl)-acrylamide (0.3 g, 1.33 mmol) was dissolved in ethanol. Pyrrolidine (0.12 ml, 1.46 mmol) was added and the mixture was heated to reflux overnight. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate. Aqueous ammonium chloride was added and the aqueous layer was extracted twice with ethyl acetate. The organics were combined, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to yield the desired product. Yield 0.24 g, 60%. LCMS method: 2, RT: 2.67 min; MI: 297-299 [M+1]. the mixture was heated to reflux overnight The solvent was removed under reduced pressure the residue was dissolved in ethyl acetate Aqueous ammonium chloride was added the aqueous layer was extracted twice with ethyl acetate dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

Procedure: This material was synthesized by the reaction of N-(4-bromophenyl)acrylamide with 4-(3-benzyloxyphenyl)-4-fluoro-3-methylpiperidine hydrochloride as described in Step 1 of Example 20. The desired compound was obtained as a light yellow solid in 65% yield.

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

Procedure: To a solution of N-(4-bromophenyl)acrylamide (340 mg, 1.50 mmol) in methanol (10 mL) was added 4-(3-benzyloxyphenyl)-4-fluoropiperidine hydrochloride (321 mg, 1.00 mmol) followed by sodium bicarbonate (840 mg, 10.0 mmol) and the resulting suspension stirred at room temperature for 52 hours. After this time the reaction was filtered and the filtrate concentrated under reduced pressure. The residue was treated with ethyl acetate (10 mL) and the resulting suspension re-filtered and concentrated under reduced pressure. The resulting solid was treated with 10% hydrogen chloride in methanol (10 mL) and the solution re-concentrated. Subsequent trituration with ethyl acetate (10 mL) afforded 3-[4-(3-benzyloxyphenyl)-4-fluoropiperidin-1-yl]-N-(4-bromophenyl)propionamide hydrochloride in 64% yield as a light yellow solid. After this time the reaction was filtered the filtrate concentrated under reduced pressure The residue was treated with ethyl acetate (10 mL) the resulting suspension re-filtered concentrated under reduced pressure The resulting solid was treated with 10% hydrogen chloride in methanol (10 mL) the solution re-concentrated