2-chloro-N-(2-chloroethyl)-N-[(4-methoxyphenyl)methyl]ethanamine

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

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

Procedure: 4-(4-but-2-ynyloxy-benzenesulfonyl)-1-(4-methoxy-benzyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outlined in Example 1. Starting from (4-but-2-ynyloxy-benzenesulfonyl)-acetic acid ethyl ester (2 g, 6.73 mmol) and bis-(2-chloro-ethyl)-(4-methoxy-benzyl)-amine (2.61 g, 8.75 mmol) and following the procedure as outlined in Example 1 (Step 6) 2.5 g of the product was isolated. Yield 2.5 g (77%); yellow oil; MS: 486 (M+H)+. was isolated

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

Procedure: 4-(4-but-2-ynyloxy-benzenesulfonyl)-1-(4-methoxy-benzyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outlined in Example 1. Starting from (4-but-2-ynyloxy-benzenesulfonyl)-acetic acid ethyl ester (2 g, 6.73 mmol) and bis-(2-chloro-ethyl)-(4-methoxy-benzyl)-amine (2.61 g, 8.75 mmol) and following the procedure as outlined in Example 1 (Step 6) 2.5 g of the product was isolated. Yield 2.5 g (77%); yellow oil; MS: 486 (M+H)+ was isolated

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

Procedure: 4-(4-but-2-ynyloxy-benzenesulfonyl)-1-(4-methoxy-benzyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outlined in Example 1. Starting from (4-but-2-ynyloxy-benzenesulfonyl)-acetic acid ethyl ester (2 g, 6.73 mmol) and bis-(2-chloro-ethyl)-(4-methoxy-benzyl)-amine (2.61 g, 8.75 mmol) and following the procedure as outlined in Example 1 (Step 6) 2.5 g of the product was isolated. Yield 2.5 g (77%); yellow oil; MS: 486 (M+H)+ was isolated

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

Procedure: A solution of 3-chloro-2-pyridylacetonitrile [prepared by the method described in JP08295663] (1.46 g, 9.57 mmol) in DMSO (19 mL) was slowly added to NaH (60% oil dispersion, 1.01 g, 25.3 mmol), and the mixture was stirred at room temperature for 1 h. A solution of N,N-bis(2-chloroethyl)-p-methoxybenzylamine (2.21 g, 8.43 mmol) in DMSO (19 mL) was added, and the resulting mixture was stirred at 75° C. for 4 h. After cooling, water (100 mL) was added, and the mixture was extracted with ethyl acetate. The organic extract was washed with brine, dried (Na2SO4), and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/2) to give 4-(3-chloro-2-pyridyl)-4-cyano-1-(4-methoxyphenyl)methylpiperidine 1 (1.91 g, 60%) as an orange oil. the resulting mixture was stirred at 75° C. for 4 h After cooling the mixture was extracted with ethyl acetate The organic extract was washed with brine dried (Na2SO4) the solvent was removed under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/2)

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

Procedure: A solution of 3-chloro-2-pyridylacetonitrile [prepared by the method described in JP08295663] (1.46 g, 9.57 mmol) in DMSO (19 mL) was slowly added to NaH (60% oil dispersion, 1.01 g, 25.3 mmol), and the mixture was stirred at room temperature for 1 h. A solution of N,N-bis(2-chloroethyl)-p-methoxybenzylamine (2.21 g, 8.43 mmol) in DMSO (19 mL) was added, and the resulting mixture was stirred at 75° C. for 4 h. After cooling, water (100 mL) was added, and the mixture was extracted with ethyl acetate. The organic extract was washed with brine, dried (Na2SO4), and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/2) to give 4-(3-chloro-2-pyridyl)-4-cyano-1-(4-methoxyphenyl)methylpiperidine 1 (1.91 g, 60%) as an orange oil. the resulting mixture was stirred at 75° C. for 4 h After cooling the mixture was extracted with ethyl acetate The organic extract was washed with brine dried (Na2SO4) the solvent was removed under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/2)

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

Procedure: A solution of 3-chloro-2-pyridylacetonitrile [prepared by the method described in JP08295663] (1.46 g, 9.57 mmol) in DMSO (19 mL) was slowly added to NaH (60% oil dispersion, 1.01 g, 25.3 mmol), and the mixture was stirred at room temperature for 1 h. A solution of N,N-bis(2-chloroethyl)-p-methoxybenzylamine (2.21 g, 8.43 mmol) in DMSO (19 ml,) was added, and the resulting mixture was stirred at 75° C. for 4 h. After cooling, water (100 mL) was added, and the mixture was extracted with ethyl acetate. The organic extract was washed with brine, dried (Na2SO4), and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/2) to give 4-(3-chloro-2-pyridyl)-4-cyano-1-(4-methoxyphenyl)methylpiperidine 1 (1.91 g, 60%) as an orange oil. the resulting mixture was stirred at 75° C. for 4 h After cooling the mixture was extracted with ethyl acetate The organic extract was washed with brine dried (Na2SO4) the solvent was removed under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/2)

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

Procedure: A solution of 3-chloro-2-pyridylacetonitrile [prepared by the method described in JP08295663] (1.46 g, 9.57 mmol) in DMSO (19 mL) was slowly added to NaH (60% oil dispersion, 1.01 g, 25.3 mmol), and the mixture was stirred at room temperature for 1 h. A solution of N,N-bis(2-chloroethyl)-p-methoxybenzylamine (2.21 g, 8.43 mmol) in DMSO (19 mL) was added, and the resulting mixture was stirred at 75° C. for 4 h. After cooling, water (100 mL) was added, and the mixture was extracted with ethyl acetate. The organic extract was washed with brine, dried (Na2SO4), and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/2) to give 4-(3-chloro-2-pyridyl)-4-cyano-1-(4-methoxyphenyl)methylpiperidine 1 (1.91 g, 60%) as an orange oil. the resulting mixture was stirred at 75° C. for 4 h After cooling the mixture was extracted with ethyl acetate The organic extract was washed with brine dried (Na2SO4) the solvent was removed under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/2)

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

Procedure: 4-(4-but-2-ynyloxy-benzenesulfonyl)-1-(4-methoxy-benzyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outlined in Example 1. Starting from (4-but-2-ynyloxy-benzenesulfonyl)-acetic acid ethyl ester (2 g, 6.73 mmol) and bis-(2-chloro-ethyl)-(4-methoxy-benzyl)-amine (2.61 g, 8.75 mmol) and following the procedure as outlined in Example 1 (Step 6) 2.5 g of the product was isolated. Yield 2.5 g (77%); yellow oil; MS: 486 (M+H)+. was isolated

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

Procedure: 4-(4-but-2-ynyloxy-benzenesulfonyl)-1-(4-methoxy-benzyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outlined in Example 1. Starting from (4-but-2-ynyloxy-benzenesulfonyl)-acetic acid ethyl ester (2 g, 6.73 mmol) and bis-(2-chloro-ethyl)-(4-methoxy-benzyl)-amine (2.61 g, 8.75 mmol) and following the procedure as outlined in Example 1 (Step 6) 2.5 g of the product was isolated. Yield 2.5 g (77%); yellow oil; MS: 486 (M+H)+. was isolated

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

Procedure: 4-(4-but-2-ynyloxy-benzenesulfonyl)-1-(4-methoxy-benzyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outlined in Example 1. Starting from (4-but-2-ynyloxy-benzenesulfonyl)-acetic acid ethyl ester (2 g, 6.73 mmol) and bis-(2-chloro-ethyl)-(4-methoxy-benzyl)-amine (2.61 g, 8.75 mmol) and following the procedure as outlined in Example 1 (Step 6) 2.5 g of the product was isolated. Yield 2.5 g (77%); yellow oil; MS: 486 (M+H)+ was isolated

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

Procedure: 4-(4-but-2-ynyloxy-benzenesulfonyl)-1-(4-methoxy-benzyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outlined in Example 1. Starting from (4-but-2-ynyloxy-benzenesulfonyl)-acetic acid ethyl ester (2 g, 6.73 mmol) and bis-(2-chloro-ethyl)-(4-methoxy-benzyl)-amine (2.61 g, 8.75 mmol) and following the procedure as outlined in Example 1 (Step 6) 2.5 g of the product was isolated. Yield 2.5 g (77%); yellow oil; MS: 486 (M+H)+ was isolated