undecan-1-amine

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

Procedure: Sodium cyanoborohydride (63 mg, 1.0 mmol) was added to a mixture of 1-(6-oxohexyl)-3,7-dimethylxanthine (150 mg, 0.5 mmol), undecylamine (0.43 mL, 2.5 mmol), 38% aqueous hydrochloric acid solution (0.2 mL, 2.5 mmol), methanol (5 mL), and tetrahydrofuran (5 mL). The resulting mixture was stirred for 48 hours. Saturated aqueous ammonium chloride solution (20 mL) was added to the stirred mixture, followed by an additional 20 minutes of stirring and addition of 30% aqueous ammonium hydroxide solution (30 mL). The mixture was extracted with 25% methanol-dichloromethane (3×35 mL) and the combined extracts dried over sodium sulfate. The solvents were evaporated under vacuum, resulting in 190 mg of 1-[5-(Undecylamino)hexyl]-3,7-dimethylxanthine (86% yield). followed by an additional 20 minutes of stirring The mixture was extracted with 25% methanol-dichloromethane (3×35 mL) the combined extracts dried over sodium sulfate The solvents were evaporated under vacuum

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

Procedure: Thiophosgene (10.9 mls, 0.14 moles) is added dropwise to a well stirred mixture of undecylamine (49.9 g, 0.29 moles) and water (400 mls). The mixture is heated to reflux following the addition. After 45 minutes the mixture is allowed to cool while potassium carbonate (20.0 g, 0.14 moles) is added in portions, and is then reheated to reflux. After three hours the mixture is cooled and the product is filtered off, triturated in 2N HCl, refiltered, rinsed with water, and dried. Recrystallization from ethylacetate gave the product (32.7 g) mp 70°-72° C. The mixture is heated to reflux the addition is added in portions to reflux After three hours the mixture is cooled the product is filtered off triturated in 2N HCl rinsed with water dried Recrystallization from ethylacetate

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

Procedure: In this example, the spacer unit is 11-amino-undecanoic acid. The spacer (411 mg, 2.04 mmol, 4 eq) is suspended in a dry organic solvent, for example tetrahydrofuran (THF). Depending on its solubility and the stability of the Raman marker unit, the suspension temperature can be varied between −78° C. and reflux. First, an auxiliary base (2.1 ml triethylamine) is added. Then, the activated marker unit in a suitable organic solvent, for example DTNB-NHS (300 mg, 0.51 mmol in 10 ml THF and 5 ml DMF), is added dropwise. Depending on the reactivity, the reaction mixture is stirred 10 to 48 h, in this case 16 h. The solvent is removed by vacuum, the remaining solid is washed with NaHSO4 solution and a suitable organic solvent. Further purification can be achieved by column chromatography, preferably on reversed phase silica (yield: 260 mg, 0.34 mmol, 67%). can be varied between −78° C. reflux The solvent is removed by vacuum the remaining solid is washed with NaHSO4 solution Further purification

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

Procedure: Sodium cyanoborohydride (63 mg, 1.0 mmol) was added to a mixture of 1-(6-oxohexyl)-3,7-dimethylxanthine (150 mg, 0.5 mmol), undecylamine (0.43 mL, 2.5 mmol), 38% aqueous hydrochloric acid solution (0.2 mL, 2.5 mmol), methanol (5 mL), and tetrahydrofuran (5 mL). The resulting mixture was stirred for 48 hours. Saturated aqueous ammonium chloride solution (20 mL) was added to the stirred mixture, followed by an additional 20 minutes of stirring and addition of 30% aqueous ammonium hydroxide solution (30 mL). The mixture was extracted with 25% methanol-dichloromethane (3×35 mL) and the combined extracts dried over sodium sulfate. The solvents were evaporated under vacuum, resulting in 190 mg of 1-[5-(Undecylamino)hexyl]-3,7-dimethylxanthine (86% yield). followed by an additional 20 minutes of stirring The mixture was extracted with 25% methanol-dichloromethane (3×35 mL) the combined extracts dried over sodium sulfate The solvents were evaporated under vacuum

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

Procedure: Sodium cyanoborohydride (63 mg, 1.0 mmol) was added to a mixture of 1-(6-oxohexyl)-3,7-dimethylxanthine (150 mg, 0.5 mmol), undecylamine (0.43 mL, 2.5 mmol), 38% aqueous hydrochloric acid solution (0.2 mL, 2.5 mmol), methanol (5 mL), and tetrahydrofuran (5 mL). The resulting mixture was stirred for 48 hours. Saturated aqueous ammonium chloride solution (20 mL) was added to the stirred mixture, followed by an additional 20 minutes of stirring and addition of 30% aqueous ammonium hydroxide solution (30 mL). The mixture was extracted with 25% methanol-dichloromethane (3×35 mL) and the combined extracts dried over sodium sulfate. The solvents were evaporated under vacuum, resulting in 190 mg of 1-[5-(Undecylamino)hexyl]-3,7-dimethylxanthine (86% yield). followed by an additional 20 minutes of stirring The mixture was extracted with 25% methanol-dichloromethane (3×35 mL) the combined extracts dried over sodium sulfate The solvents were evaporated under vacuum

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

Procedure: To a solution of (S)-2-(9H-fluoren-9-ylmethoxycarbonyl-amino)succinic acid (150 mg, 0.36 mmol), BOP reagent (162 mg, 0.36 mmol) and HOBT hydrate (56 mg, 0.36 mmol) in N,N-dimethylformamide (0.2 ml) was added N,N-diisopropylethylamine (64 μl, 0.36 mmol). After being stirred for 30 min at room temperature, 1-aminoundecane (79 μl, 0.37 mmol) was added. The mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with water and extracted with Et2O. The combined extracts were washed with water, dried over anhydrous sodium sulfate, filtered and concentrated. Purification of the residue by silica gel column chromatography (using n-hexane:ethyl acetate =3:1 as an eluent ) gave (S)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-N-undecylsuccinamic acid tert-butyl ester (169 mg, 82% yield) as a colorless amorphous solid. The mixture was stirred at room temperature for 3 h extracted with Et2O The combined extracts were washed with water dried over anhydrous sodium sulfate filtered concentrated Purification of the residue by silica gel column chromatography (

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

Procedure: To a solution of (S)-2-(9H-fluoren-9-ylmethoxycarbonyl-amino)succinic acid (150 mg, 0.36 mmol), BOP reagent (162 mg, 0.36 mmol) and HOBT hydrate (56 mg, 0.36 mmol) in N,N-dimethylformamide (0.2 ml) was added N,N-diisopropylethylamine (64 μl, 0.36 mmol). After being stirred for 30 min at room temperature, 1-aminoundecane (79 μl, 0.37 mmol) was added. The mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with water and extracted with Et2O. The combined extracts were washed with water, dried over anhydrous sodium sulfate, filtered and concentrated. Purification of the residue by silica gel column chromatography (using n-hexane:ethyl acetate =3:1 as an eluent ) gave (S)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-N-undecylsuccinamic acid tert-butyl ester (169 mg, 82% yield) as a colorless amorphous solid. The mixture was stirred at room temperature for 3 h extracted with Et2O The combined extracts were washed with water dried over anhydrous sodium sulfate filtered concentrated Purification of the residue by silica gel column chromatography (

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

Procedure: Reduction of undecanenitrile in n-propylamine, ethylenediamine, and t-butanol. Lithium, (0.28 g, 40 mmol) in small pieces, was added to undecanenitrile (0.775 g, 4.63 mmol) in n-propylamine (10 mL), ethylenediamine (1.5 g, 25 mmol) and t-butanol (2.22 g, 30 mmol). After 20 min, the temperature increased to 55° and decreased slowly. After another 2 hr, the reaction mixture was poured onto a slurry of water (25 mL) and ice (25 g). The reaction mixture was extracted twice with ether (25 mL and 50 mL). The ether extract was analyzed by glpc using ethyl benzoate as internal standard. Glpc analysis showed n-decane in 17% yield and undecylamine in 83% yield. A similiar reaction using methanol in place of t-butanol in the same mole ratio gave the same percentages of n-decane and undecaneamine. the temperature increased to 55° After another 2 hr The reaction mixture was extracted twice with ether (25 mL and 50 mL) The ether extract A similiar reaction

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

Procedure: Sodium cyanoborohydride (63 mg, 1.0 mmol) was added to a mixture of 1-(6-oxohexyl)-3,7-dimethylxanthine (150 mg, 0.5 mmol), undecylamine (0.43 mL, 2.5 mmol), 38% aqueous hydrochloric acid solution (0.2 mL, 2.5 mmol), methanol (5 mL), and tetrahydrofuran (5 mL). The resulting mixture was stirred for 48 hours. Saturated aqueous ammonium chloride solution (20 mL) was added to the stirred mixture, followed by an additional 20 minutes of stirring and addition of 30% aqueous ammonium hydroxide solution (30 mL). The mixture was extracted with 25% methanol-dichloromethane (3×mL) and the combined extracts dried over sodium sulfate. The solvents were evaporated under vacuum, resulting in 190 mg of 1-[5-(Undecylamino)hexyl]-3,7-dimethylxanthine (86% yield). followed by an additional 20 minutes of stirring The mixture was extracted with 25% methanol-dichloromethane (3×mL) the combined extracts dried over sodium sulfate The solvents were evaporated under vacuum

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

Procedure: Thiophosgene (10.9 mls, 0.14 moles) is added dropwise to a well stirred mixture of undecylamine (49.9 g, 0.29 moles) and water (400 mls). The mixture is heated to reflux following the addition. After 45 minutes the mixture is allowed to cool while potassium carbonate (20.0 g, 0.14 moles) is added in portions, and is then reheated to reflux. After three hours the mixture is cooled and the product is filtered off, triturated in 2N HCl, refiltered, rinsed with water, and dried. Recrystallization from ethylacetate gave the product (32.7 g) mp 70°-72° C. The mixture is heated to reflux the addition is added in portions to reflux After three hours the mixture is cooled the product is filtered off triturated in 2N HCl rinsed with water dried Recrystallization from ethylacetate

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

Procedure: In this example, the spacer unit is 11-amino-undecanoic acid. The spacer (411 mg, 2.04 mmol, 4 eq) is suspended in a dry organic solvent, for example tetrahydrofuran (THF). Depending on its solubility and the stability of the Raman marker unit, the suspension temperature can be varied between −78° C. and reflux. First, an auxiliary base (2.1 ml triethylamine) is added. Then, the activated marker unit in a suitable organic solvent, for example DTNB-NHS (300 mg, 0.51 mmol in 10 ml THF and 5 ml DMF), is added dropwise. Depending on the reactivity, the reaction mixture is stirred 10 to 48 h, in this case 16 h. The solvent is removed by vacuum, the remaining solid is washed with NaHSO4 solution and a suitable organic solvent. Further purification can be achieved by column chromatography, preferably on reversed phase silica (yield: 260 mg, 0.34 mmol, 67%). can be varied between −78° C. reflux The solvent is removed by vacuum the remaining solid is washed with NaHSO4 solution Further purification

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

Procedure: Sodium cyanoborohydride (63 mg, 1.0 mmol) was added to a mixture of 1-(6-oxohexyl)-3,7-dimethylxanthine (150 mg, 0.5 mmol), undecylamine (0.43 mL, 2.5 mmol), 38% aqueous hydrochloric acid solution (0.2 mL, 2.5 mmol), methanol (5 mL), and tetrahydrofuran (5 mL). The resulting mixture was stirred for 48 hours. Saturated aqueous ammonium chloride solution (20 mL) was added to the stirred mixture, followed by an additional 20 minutes of stirring and addition of 30% aqueous ammonium hydroxide solution (30 mL). The mixture was extracted with 25% methanol-dichloromethane (3×35 mL) and the combined extracts dried over sodium sulfate. The solvents were evaporated under vacuum, resulting in 190 mg of 1-[5-(Undecylamino)hexyl]-3,7-dimethylxanthine (86% yield). followed by an additional 20 minutes of stirring The mixture was extracted with 25% methanol-dichloromethane (3×35 mL) the combined extracts dried over sodium sulfate The solvents were evaporated under vacuum