tert-butyl 2-(2-hydroxyethyl)piperidine-1-carboxylate

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

Procedure: Following a procedure similar to that described in Example 36(a), 1.00 g of 2-[2-(3-methoxyphenyl)ethyl]phenol (prepared as described in Preparation 20), 1.51 g of 1-t-butoxycarbonyl-2-(2-hydroxyethyl)piperidine, 1.72 g of triphenylphosphine and 1.14 g of diethyl azodicarboxylate were reacted in 20 ml of methylene chloride. The mixture was then worked up as described in Example 36(a), and the crude product thus obtained was purified by column chromatography through silica gel, using a 4:1 by volume mixture of hexane and ethyl acetate as the eluent, to give 0.630 g (yield 32%) of the title compound as a colorless oil. the crude product thus obtained was purified by column chromatography through silica gel by volume mixture of hexane and ethyl acetate as the eluent

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

Procedure: Following a procedure similar to that described in Example 36(a), 1.00 g of 2-[2-(3-methoxyphenyl)ethyl]phenol (prepared as described in Preparation 20), 1.51 g of 1-t-butoxycarbonyl-2-(2-hydroxyethyl)piperidine, 1.72 g of triphenylphosphine and 1.14 g of diethyl azodicarboxylate were reacted in 20 ml of methylene chloride. The mixture was then worked up as described in Example 36(a), and the crude product thus obtained was purified by column chromatography through silica gel, using a 4:1 by volume mixture of hexane and ethyl acetate as the eluent, to give 0.630 g (yield 32%) of the title compound as a colorless oil. the crude product thus obtained was purified by column chromatography through silica gel by volume mixture of hexane and ethyl acetate as the eluent

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

Procedure: Following a procedure similar to that described in Example 5(a), 1.69 g of 2-(4-phenylbutyl)phenol (prepared as described in Preparation 3), 1.72 g of 1-t-butoxycarbonyl-2-(2-hydroxyethyl)piperidine, 5.9 g of triphenylphosphine and 3.92 g of diethyl azodicarboxylate were reacted in 75 ml of methylene chloride. The crude oily product, extracted as described in Example 5(a), was purified by column chromatography through silica gel, using a 5:1 by volume mixture of hexane and ethyl acetate as the eluent, to give 1.13 g (yield 34%) of the title compound as an oil. The crude oily product, extracted was purified by column chromatography through silica gel by volume mixture of hexane and ethyl acetate as the eluent

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

Procedure: To a slurry of lithium aluminum hydride (580 mg in 65 mL dry diethyl ether) at 0° C. was added dropwise a solution of 2-(methoxycarbonylmethyl)piperidine-1-carboxylic acid tert-butyl ester (5.47 g in 40 mL dry diethyl ether) over a period of 30 minutes. The reaction was allowed to continue at 0° C. for an additional hour, at which time it was quenched by the careful addition of 0.58 mL water followed by 0.58 mL 2N sodium hydroxide and 1.8 mL water. The resulting suspension was stirred vigourously for 30 minutes then filtered through diatomaceous earth. The filtrate was concentrated in vacuo and the residue purified by flash chromatography on silica gel (hexane:ethyl acetate, 6:4) to give the title compound (4.61 g). to continue at 0° C. for an additional hour, at which time it was quenched by the careful addition of 0.58 mL water then filtered through diatomaceous earth The filtrate was concentrated in vacuo the residue purified by flash chromatography on silica gel (hexane:ethyl acetate, 6:4)

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

Procedure: To a solution of 7-chloro-4-hydroxy-6-nitro-3-thiophen-2-yl-1H-quinolin-2-one (50 mg in 2.5 mL of tetrahydrofuran) at 0° C. was added 44 mg of 2-(2-hydroxyethyl)-piperidine-1-carboxylic acid tert-butyl ester and 63 mg of triphenylphosphine followed by 0.04 mL of diethyl azodicarboxylate and the mixture warmed to room temperature. After 24 hours, the solvents were removed in vacuo and the residue purified by flash chromatography on silica gel (hexane:ethyl acetate, 90:10; then 80:20; then 60:40) to give the title compound (44 mg). the solvents were removed in vacuo the residue purified by flash chromatography on silica gel (hexane

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

Procedure: To a solution of 2-(2-hydroxyethyl)-piperidine-1-carboxylic acid tert-butyl ester (10 g in 450 mL dry tetrahydrofuran) was added 22.3 g of 7-chloro-3-(3,5-dimethylphenyl)-4-hydroxy-6-iodo-1H-quinolin-2-one followed by 13.7 g of triphenylphosphine and the mixture stirred at room temperature. To this was added 8.2 mL of diethyl azodicarboxylate (DEAD) and stirring was continued for 72 hours. At this time the solvents were removed to a minimum volume in vacuo and the mixture filterd through a silica gel pad to remove the phosphine by-products. The filtrate was concentrated in vacuo to provide the partially purified title compound (17.5 g). stirring At this time the solvents were removed to a minimum volume in vacuo the mixture filterd through a silica gel pad to remove the phosphine by-products The filtrate was concentrated in vacuo to provide the partially purified title compound (17.5 g)

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

Procedure: To a solution of 6-allyl-7-chloro-3-(3,5-dimethylphenyl)-4-hydroxy-1H-quinolin-2-one (960 mg in 30 mL of tetrahydrofuran) at 0° C. was added 615 mg of 2-(2-hydroxyethyl)-piperidine-1-carboxylic acid tert-butyl ester and 1.04 g of triphenylphosphine followed by 0.56 mL of diethyl azodicarboxylate and the mixture warmed to room temperature. After 20 hours, the solvents were removed in vacuo and the residue purified by flash chromatography on silica gel (hexane:ethylacetate, 85:15; then 80:20; then 90:10) to give the title compound (1.19 g). the solvents were removed in vacuo the residue purified by flash chromatography on silica gel (hexane

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

Procedure: To a solution of 2-(2-hydroxyethyl)-piperidine-1-carboxylic acid tert-butyl ester (0.864 g in 38 mL dry tetrahydrofuran) was added 1.56 g of 7-chloro-3-(3,5-dimethylphenyl)-4-hydroxy-6-nitro- 1H-quinolin-2-one followed by 1.19 g of triphenylphosphine and the mixture stirred at room temperature. To this was added 0.72 mL of diethyl azodicarboxylate (DEAD) and stirring was continued for 64 hours. At this time the solvents were removed in vacuo and the residue purified by flash chromatography on silica gel (hexane:ethyl acetate, 6:4) to give the title compound (1.56 g). stirring At this time the solvents were removed in vacuo the residue purified by flash chromatography on silica gel (hexane:ethyl acetate, 6:4)

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

Procedure: To a solution of 6-allyl-7-chloro-3-(3,5-dimethylphenyl)-4-hydroxy-1H-quinolin-2-one (960 mg in 30 mL of tetrahydrofuran) at 0° C. was added 615 mg of 2-(2-hydroxyethyl)-piperidine-1-carboxylic acid tert-butyl ester and 1.04 g of triphenylphosphine followed by 0.56 mL of diethyl azodicarboxylate and the mixture warmed to room temperature. After 20 hours, the solvents were removed in vacuo and the residue purified by flash chromatography on silica gel (hexane:ethyl acetate, 85:15; then 80:20; then 90:10) to give 1.19 g of the title compound. the solvents were removed in vacuo the residue purified by flash chromatography on silica gel (hexane

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

Procedure: To a solution of 3-(3-bromophenyl)-7-chloro-4-hydroxy-6-nitro-1H-quinolin-2-one (100 mg in 4.0 mL of tetrahydrofuran) at 0° C. was added 64 mg of 2-(2-hydroxyethyl)-piperidine-1-carboxylic acid tert-butyl ester and 93 mg of triphenylphosphine followed by 0.050 mL of diethyl azodicarboxylate and the mixture warmed to room temperature. After 20 hours, the solvents were removed in vacuo and the residue purified by flash chromatography on silica gel (hexane:ethylacetate, 2:1) to give the title compound (92 mg). the solvents were removed in vacuo the residue purified by flash chromatography on silica gel (hexane:ethylacetate, 2:1)

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

Procedure: 2-(2-Hydroxyethyl)piperidine-1-carboxylic acid tert-butyl ester (229 mg) obtained from Referential Example 77 and triethylamine (209 μL) were dissolved in methylene chloride (5 mL) To the resultant solution, methanesulfonyl chloride (116 μL) was added at room temperature, followed by stirring for 30 minutes. The residue obtained by removal through evaporation of the reaction solvent under reduced pressure was partitioned between water and methylene chloride. The organic layer was sequentially washed with water and saturated brine, and then dried over sodium sulfate anhydrate, followed by filtration. The solvent was evaporated under reduced pressure, to thereby give the title compound in the form of crystals (288 mg, 93%). was added at room temperature The residue obtained by removal through evaporation of the reaction solvent under reduced pressure was partitioned between water and methylene chloride The organic layer was sequentially washed with water and saturated brine dried over sodium sulfate anhydrate followed by filtration The solvent was evaporated under reduced pressure

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

Procedure: To a slurry of lithium aluminum hydride (580 mg in 65 mL dry diethyl ether) at 0° C. was added dropwise a solution of 2-(methoxycarbonylmethyl)piperidine-1-carboxylic acid tert-butyl ester (5.47 g in 40 mL dry diethyl ether) over a period of 30 minutes. The reaction was allowed to continue at 0° C. for an additional hour, at which time it was quenched by the careful addition of 0.58 mL water followed by 0.58 mL 2N sodium hydroxide and 1.8 mL water. The resulting suspension was stirred vigourously for 30 minutes then filtered through diatomaceous earth. The filtrate was concentrated in vacuo and the residue purified by flash chromatography on silica gel (hexane:ethyl acetate, 6:4) to give the title compound (4.61 g). to continue at 0° C. for an additional hour, at which time it was quenched by the careful addition of 0.58 mL water then filtered through diatomaceous earth The filtrate was concentrated in vacuo the residue purified by flash chromatography on silica gel (hexane:ethyl acetate, 6:4)