pent-4-ynal

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

Procedure: To a solution of pent-4-ynal (6.99 g, 85.1 mmol) dissolved in methylene chloride (85 mL) was added 1,3-propanedithiol (8.54 mL, 85.1 mmol). The solution was stirred at room temperature for 1 hour and then cooled to -20° C. Boron trifluoride etherate (10.46 mL, 85.1 mmol) was added and, after warming to room temperature, the solution was stirred for 16 hours. The solution was washed with water (2×20 mL) and the aqueous extract was washed with additional methylene chloride (2×40 mL). The combined organic extracts were washed with 10% potassium hydroxide solution (4×30 mL) and the aqueous extract was washed with additional methylene chloride (2×40 mL). The combined organic extracts were washed with 10% potassium hydroxide solution (4×30 mL) and the aqueous extract was back-extracted with methylene chloride (2×40 mL). The combined organic extracts were washed with brine (2×40 mL) and dried (K2CO3). The solvent was removed by rotary evaporation to afford 9.14 g (62%) of 2-(but-3-ynyl)-1,3-dithiane as a pale yellow oil. 1H NMR (CDCl3)δ: 4.2 (t, 1H), 3.1-2.8 (m, 4H), 2.6-2.4 (m, 1H), 2.3-2.0 (m, 6H); IR (neat): 3286, 2908, 1421, 1272, 907 cm-1 ; GC retention time=3.11 min (88% area); TLC (silica gel, 90% hexane: 10% ethyl acetate) Rf=0.74. cooled to -20° C after warming to room temperature the solution was stirred for 16 hours The solution was washed with water (2×20 mL) the aqueous extract was washed with additional methylene chloride (2×40 mL) The combined organic extracts were washed with 10% potassium hydroxide solution (4×30 mL) the aqueous extract was washed with additional methylene chloride (2×40 mL) The combined organic extracts were washed with 10% potassium hydroxide solution (4×30 mL) the aqueous extract was back-extracted with methylene chloride (2×40 mL) The combined organic extracts were washed with brine (2×40 mL) dried (K2CO3) The solvent was removed by rotary evaporation

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

Procedure: To a solution of pent-4-ynal (6.99 g, 85.1 mmol) dissolved in methylene chloride (85 mL) was added 1,3-propanedithiol (8.54 mL, 85.1 mmol). The solution was stirred at room temperature for 1 hour and then cooled to -20° C. Boron trifluoride etherate (10.46 mL, 85.1 mmol) was added and, after warming to room temperature, the solution was stirred for 16 hours. The solution was washed with water (2×20 mL) and the aqueous extract was washed with additional methylene chloride (2×40 mL). The combined organic extracts were washed with 10% potassium hydroxide solution (4×30 mL) and the aqueous extract was washed with additional methylene chloride (2×40 mL). The combined organic extracts were washed with 10% potassium hydroxide solution (4×30 mL) and the aqueous extract was back-extracted with methylene chloride (2×40 mL). The combined organic extracts were washed with brine (2×40 mL) and dried (K2CO3). The solvent was removed by rotary evaporation to afford 9.14 g (62%) of 2-(but-3-ynyl)-1,3-dithiane as a pale yellow oil. 1H NMR (CDCl3)δ: 4.2 (t, 1H), 3.1-2.8 (m, 4H), 2.6-2.4 (m, 1H), 2.3-2.0 (m, 6H); IR (neat): 3286, 2908, 1421, 1272, 907 cm-1 ; GC retention time=3.11 min (88% area); TLC (silica gel, 90% hexane: 10% ethyl acetate) Rf=0.74. cooled to -20° C after warming to room temperature the solution was stirred for 16 hours The solution was washed with water (2×20 mL) the aqueous extract was washed with additional methylene chloride (2×40 mL) The combined organic extracts were washed with 10% potassium hydroxide solution (4×30 mL) the aqueous extract was washed with additional methylene chloride (2×40 mL) The combined organic extracts were washed with 10% potassium hydroxide solution (4×30 mL) the aqueous extract was back-extracted with methylene chloride (2×40 mL) The combined organic extracts were washed with brine (2×40 mL) dried (K2CO3) The solvent was removed by rotary evaporation

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

Procedure: To a solution of pent-4-ynal (6.99 g, 85.1 mmol) dissolved in methylene chloride (85 mL) was added 1,3-propanedithiol (8.54 mL, 85.1 mmol). The solution was stirred at room temperature for 1 hour and then cooled to -20° C. Boron trifluoride etherate (10.46 mL, 85.1 mmol) was added and, after warming to room temperature, the solution was stirred for 16 hours. The solution was washed with water (2×20 mL) and the aqueous extract was washed with additional methylene chloride (2×40 mL). The combined organic extracts were washed with 10% potassium hydroxide solution (4×30 mL) and the aqueous extract was washed with additional methylene chloride (2×40 mL). The combined organic extracts were washed with 10% potassium hydroxide solution (4×30 mL) and the aqueous extract was back-extracted with methylene chloride (2×40 mL). The combined organic extracts were washed with brine (2×40 mL) and dried (K2CO3). The solvent was removed by rotary evaporation to afford 9.14 g (62%) of 2-(but-3-ynyl)-1,3-dithiane as a pale yellow oil. 1H NMR (CDCl3)δ: 4.2 (t, 1H), 3.1-2.8 (m, 4H), 2.6-2.4 (m, 1H), 2.3-2.0 (m, 6H); IR (neat): 3286, 2908, 1421, 1272, 907 cm-1 ; GC retention time=3.11 min (88% area); TLC (silica gel, 90% hexane: 10% ethyl acetate) Rf=0.74. cooled to -20° C after warming to room temperature the solution was stirred for 16 hours The solution was washed with water (2×20 mL) the aqueous extract was washed with additional methylene chloride (2×40 mL) The combined organic extracts were washed with 10% potassium hydroxide solution (4×30 mL) the aqueous extract was washed with additional methylene chloride (2×40 mL) The combined organic extracts were washed with 10% potassium hydroxide solution (4×30 mL) the aqueous extract was back-extracted with methylene chloride (2×40 mL) The combined organic extracts were washed with brine (2×40 mL) dried (K2CO3) The solvent was removed by rotary evaporation

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

Procedure: To a solution of (9H-fluoren-9-yl)methyl (2-amino-4-methoxy-2-(2-methoxyethyl)butyl)carbamate (G23, 186 mg) and 4-pentynal (42 mg) in methylene chloride (5 mL), sodium triacetoxyborohydride (247 mg) and acetic acid (26 μL) were added at room temperature, and the mixture was stirred at the same temperature for 3 hours. To the reaction mixture, ethyl acetate and saturated aqueous sodium hydrogencarbonate were added. The organic layer was separated, washed with saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 60 to 0% hexane in ethyl acetate) to obtain (9H-fluoren-9-yl)methyl (4-methoxy-2-(2-methoxyethyl)-2-((4-pentyn-1-yl)amino)butyl)carbamate (G24, 102 mg). The organic layer was separated washed with saturated aqueous sodium chloride dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography (eluent, 60 to 0% hexane in ethyl acetate)

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

Procedure: To a solution of benzyl ((4-aminotetrahydro-2H-pyran-4-yl)methyl)carbamate (G17, 106 mg) and 4-pentynal (34 mg) in methylene chloride (4 mL), sodium triacetoxyborohydride (205 mg) and acetic acid (22 μL) were added at room temperature, and the mixture was stirred at the same temperature for 2 hours. To the reaction mixture, ethyl acetate and saturated aqueous sodium hydrogencarbonate were added. The organic layer was separated, washed with saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 100 to 0% hexane in ethyl acetate) to obtain benzyl ((4-((4-pentyn-1-yl)amino)tetrahydro-2H-pyran-4-yl)methyl)carbamate (G18, 74 mg). The organic layer was separated washed with saturated aqueous sodium chloride dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography (eluent, 100 to 0% hexane in ethyl acetate)

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

Procedure: To a solution of 4-pentynal (631 mg) synthesized according to the method described in U.S. Pat. No. 4,877,779 A1 and tert-butyl (2-amino-2-methylpropyl)carbamate (328 mg) in methylene chloride (10 mL), sodium triacetoxyborohydride (921 mg) and acetic acid (99 μL) were added at room temperature, and the mixture was stirred at the same temperature for 2 hours. To the reaction mixture, ethyl acetate and saturated aqueous sodium hydrogencarbonate were added. The organic layer was separated, washed with saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 100 to 80% ethyl acetate in methanol) to obtain tert-butyl (2-methyl-2-((4-pentyn-1-yl)amino)propyl)carbamate (G7, 172 mg). The organic layer was separated washed with saturated aqueous sodium chloride dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography (eluent, 100 to 80% ethyl acetate in methanol)

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

Procedure: To a solution of 4-pentynal (631 mg) synthesized according to the method described in U.S. Pat. No. 4,877,779 A1 and tert-butyl (2-amino-2-methylpropyl)carbamate (328 mg) in methylene chloride (10 mL), sodium triacetoxyborohydride (921 mg) and acetic acid (99 μL) were added at room temperature, and the mixture was stirred at the same temperature for 2 hours. To the reaction mixture, ethyl acetate and saturated aqueous sodium hydrogencarbonate were added. The organic layer was separated, washed with saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 100 to 80% ethyl acetate in methanol) to obtain tert-butyl (2-methyl-2-((4-pentyn-1-yl)amino)propyl)carbamate (G7, 172 mg). The organic layer was separated washed with saturated aqueous sodium chloride dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography (eluent, 100 to 80% ethyl acetate in methanol)