4-(methylamino)butan-1-ol

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

Procedure: To a 250 mL round bottom flask, charged with 3.00 g (28.5 mmol) of N-methyl-4-aminobutanol in 75 mL of dioxane, was added 5 mL of triethylamine (35.4 mmol) followed by 7.85 g (31.9 mmol) of BOC-ON, 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile. The mixture was stirred at room temperature for 20 h and then concentrated via rotary evaporation. The residue was chromatographed on silica gel, eluting first with 20% ethyl acetate/hexane, then with 40% ethyl acetate/hexane, and finally with 75% ethyl/hexane. The fractions containing product were combined and concentrated via rotary evaporation to afford 4.85 g of the product (32) as a near colorless oil (84%): 1H-NMR (CDCl3) d 3.65 (2H, t), 3.23 (2H, t), 2.81 (3H, s), 1.67-1.45 (4H, m), and 1.42 (9H, s) ppm. concentrated via rotary evaporation The residue was chromatographed on silica gel eluting first with 20% ethyl acetate/hexane The fractions containing product concentrated via rotary evaporation

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5 g 4-(Methylamino)butan-1-ol (0.049 mol) is slowly added to 15 g HNO3 (100%, 0.24 mol) at −10° C., care being taken that the temperature does not rise above 10° C. The mixture is stirred for 10 min at 0° C., then poured on ice (15 g) and stirred for 2 h at room temperature. 33 g 2-Butanol is added slowly at 0° C., the obtained mixture (pH 0-1) neutralised (to pH 6) with 15.6 g NaHCO3 at 0° C., filtered and the organic phase dried over MgSO4. 1.2 g Norrit 2× is added, the mixture filtered, and the filtrate evaporated to give 5.4 g (52%) N-methyl-N-(4-nitroxybutyl)ammonium nitrate. 1H-NMR (200 MHz, DMSO-d6): 1.56-1.78 (m, 4H); 2.54 (t, J=5.5, 3H); 2.84-2.97 (m, 2H); 4.52 (t, J=5.9, 2H); 8.30 (br. s, 2H). does not rise above 10° C poured on ice (15 g) stirred for 2 h at room temperature at 0° C. filtered the organic phase dried over MgSO4 1.2 g Norrit 2× is added the mixture filtered the filtrate evaporated

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

Procedure: To a 250 mL round bottom flask, charged with 3.00 g (28.5 mmol) of N-methyl-4-aminobutanol in 75 mL of dioxane, was added 5 mL of triethylamine (35.4 mmol) followed by 7.85 g (31.9 mmol) of BOC-ON, 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile. The mixture was stirred at room temperature for 20 h and then concentrated via rotary evaporation. The residue was chromatographed on silica gel, eluting first with 20% ethyl acetate/hexane, then with 40% ethyl acetate/hexane, and finally with 75% ethyl/hexane. The fractions containing product were combined and concentrated via rotary evaporation to afford 4.85 g of the product (32) as a near colorless oil (84%): 1H-NMR (CDCl3) d 3.65 (2H, t), 3.23 (2H, t), 2.81 (3H, s), 1.67-1.45 (4H, m), and 1.42 (9H, s) ppm. concentrated via rotary evaporation The residue was chromatographed on silica gel eluting first with 20% ethyl acetate/hexane The fractions containing product concentrated via rotary evaporation

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

Procedure: To a 250 mL round bottom flask, charged with 3.00 g (28.5 mmol) of N-methyl-4-aminobutanol in 75 mL of dioxane, was added 5 mL of triethylamine (35.4 mmol) followed by 7.85 g (31.9 mmol) of BOC-ON, 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile. The mixture was stirred at room temperature for 20 h and then concentrated via rotary evaporation. The residue was chromatographed on silica gel, eluting first with 20% ethyl acetate/hexane, then with 40% ethyl acetate/hexane, and finally with 75% ethyl/hexane. The fractions containing product were combined and concentrated via rotary evaporation to afford 4.85 g of the product (32) as a near colorless oil (84%): 1H-NMR (CDCl3) d 3.65 (2H, t), 3.23 (2H, t), 2.81 (3H, s), 1.67-1.45 (4H, m), and 1.42 (9H, s) ppm. concentrated via rotary evaporation The residue was chromatographed on silica gel eluting first with 20% ethyl acetate/hexane The fractions containing product concentrated via rotary evaporation

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

Procedure: To a 250 mL round bottom flask, charged with 10.0 g (96.9 mmol) of the amine, 4-methylaminobutanol, in 100 mL of dry methanol, was added 17.5 mL (147 mmol) of ethyl trifluoroacetate. The mixture was stirred at room temperature for 24 hours and then concentrated to afford 18.55 g of the product as a near colorless oil (96%): 1H—NMR (200 MHz, D2O); 3.63 and 3.50 (2t's, 4H), 3.20 and 3.05 (d and s, 3H), and 1.82-1.47 (m, 4H) ppm. concentrated

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

Procedure: To a 250 mL round bottom flask, charged with 10.0 g (96.9 mmol) of the amine, 4-methylaminobutanol, in 100 mL of dry methanol, was added 17.5 mL (147 mmol) of ethyl trifluoroacetate. The mixture was stirred at room temperature for 24 hours and then concentrated to afford 18.55 g of the product as a near colorless oil (96%): 1H-NMR (200 MHz, D2O); 3.63 and 3.50 (2t's, 4H), 3.20 and 3.05 (d and s, 3H), and 1.82-1.47 (m, 4H) ppm. concentrated

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

Procedure: To a 250 mL round bottom flask, charged with 10.0 g (96.9 mmol) of the amine, 4-methylaminobutanol, in 100 mL of dry methanol, was added 17.5 mL (147 mmol) of ethyl trifluoroacetate. The mixture was stirred at room temperature for 24 hours and then concentrated to afford 18.55 g of the product as a near colorless oil (96%): 1H-NMR (200 MHz, D2O); 3.63 and 3.50 (2t's, 4H), 3.20 and 3.05 (d and s, 3H), and 1.82-1.47 (m, 4H) ppm. concentrated

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

Procedure: The compound (400 mg, 0.576 mmol) obtained in Example 1j was dissolved in dichloromethane (30 mL), triethylamine (0.12 mL, 1.04 mmol) and pivaloyl chloride (0.11 mL, 0.864 mmol) were added under ice cooling, and the mixture was stirred at the same temperature under a nitrogen atmosphere for 15 minutes. Subsequently, a solution of 4-(methylamino)butan-1-ol (178 mg, 1.73 mmol) in dichloromethane (2 mL) was added under ice cooling, and the mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours. After the reaction was completed, a saturated aqueous sodium hydrogencarbonate solution was added, and ethyl acetate was further added to separate the layers. The resulting organic layer was separated, washed with saturated sodium chloride solution, and then dried with anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by NH silica gel column chromatography (hexane:ethyl acetate, 10:1, v/v) to give the title compound (347 mg; yield, 77%) as a colorless oily substance. the mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours to separate the layers The resulting organic layer was separated washed with saturated sodium chloride solution dried with anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by NH silica gel column chromatography (hexane:ethyl acetate, 10:1, v/v)

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

Procedure: The compound (400 mg, 0.576 mmol) obtained in Example 1j was dissolved in dichloromethane (30 mL), triethylamine (0.12 mL, 1.04 mmol) and pivaloyl chloride (0.11 mL, 0.864 mmol) were added under ice cooling, and the mixture was stirred at the same temperature under a nitrogen atmosphere for 15 minutes. Subsequently, a solution of 4-(methylamino)butan-1-ol (178 mg, 1.73 mmol) in dichloromethane (2 mL) was added under ice cooling, and the mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours. After the reaction was completed, a saturated aqueous sodium hydrogencarbonate solution was added, and ethyl acetate was further added to separate the layers. The resulting organic layer was separated, washed with saturated sodium chloride solution, and then dried with anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by NH silica gel column chromatography (hexane:ethyl acetate, 10:1, v/v) to give the title compound (347 mg; yield, 77%) as a colorless oily substance. the mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours to separate the layers The resulting organic layer was separated washed with saturated sodium chloride solution dried with anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by NH silica gel column chromatography (hexane:ethyl acetate, 10:1, v/v)

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

Procedure: To a 250 mL round bottom flask, charged with 10.0 g (96.9 mmol) of the amine, 4-methylaminobutanol, in 100 mL of dry methanol, was added 17.5 mL (147 mmol) of ethyl trifluoroacetate. The mixture was stirred at room temperature for 24 hours and then concentrated to afford 18.55 g of the product as a near colorless oil (96%): 1H-NMR (200 MHz, D2O); 3.63 and 3.50 (2t's, 4H), 3.20 and 3.05 (d and s, 3H), and 1.82-1.47 (m, 4H) ppm. concentrated

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

Procedure: To a 250 mL round bottom flask, charged with 10.0 g (96.9 mmol) of the amine, 4-methylaminobutanol, in 100 mL of dry methanol, was added 17.5 mL (147 mmol) of ethyl trifluoroacetate. The mixture was stirred at room temperature for 24 hours and then concentrated to afford 18.55 g of the product as a near colorless oil (96%): 1H-NMR (200 MHz, D2O); 3.63 and 3.50 (2t's, 4H), 3.20 and 3.05 (d and s, 3H), and 1.82-1.47 (m, 4H) ppm. concentrated

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

Procedure: To a 250 mL round bottom flask, charged with 10.0 g (96.9 mmol) of the amine (6) in 100 mL of dry methanol, was added 17.5 mL (147 mmol) of ethyl trifluoroacetate. The mixture was stirred at room temperature for 24 h and then concentrated to afford 18.55 g of the product (7) as a near colorless oil (96%): 1H-NMR (200 MHz, D2O); 3.63 and 3.50 (2t's, 4H), 3.20 and 3.05 (d and s, 3H), 1.82-1.47 (m, 4H) ppm. concentrated