2-(dibenzylamino)ethanol

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

Procedure: Dibenzyl-[2-(3-benzyloxy-propoxy)-ethyl]-amine (860 mg) was prepared by following General Procedure W starting from toluene-4-sulfonic acid 3-benzyloxy-propyl ester (1.33 g), N,N-dibenzyl-2-aminoethanol (1.0 g), 50% aqueous sodium hydroxide solution (1.66 g in 1.66 mL of water), and tetrabutylammonium hydrogen sulfate (141 mg).

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

Procedure: To N,N-dibenzyl-2-aminoethanol (80.68 g) were added cyclohexane (500 ml) and DMF (12.9 ml), and thereto was added dropwise thionyl bromide (83.4 g). The mixture was stirred for 15 hours, and to the reaction solution was added an saturated aqueous sodium hydrogen carbonate solution in an ice-bath, and the mixture was extracted with ethyl acetate. The organic layer was washed with water (three times) and saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound (72.1 g). the mixture was extracted with ethyl acetate The organic layer was washed with water (three times) and saturated aqueous sodium chloride solution dried over sodium sulfate filtered concentrated under reduced pressure

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

Procedure: To N,N-dibenzyl-2-aminoethanol (80.68 g) were added cyclohexane (500 ml) and DMF (12.9 ml), and thereto was added dropwise thionyl bromide (83.4 g). The mixture was stirred for 15 hours, and to the reaction solution was added an saturated aqueous sodium hydrogen carbonate solution in an ice-bath, and the mixture was extracted with ethyl acetate. The organic layer was washed with water (three times) and saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound (72.1 g). the mixture was extracted with ethyl acetate The organic layer was washed with water (three times) and saturated aqueous sodium chloride solution dried over sodium sulfate filtered concentrated under reduced pressure

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

Procedure: To a vigorously stirred solution of 6.7 ml (1.12 mol, 1 equiv.) ethanolamine in 120 ml of (1/1) MeOH/H2O were added 7.2 g (1.8 mol, 1.6 equiv.) of sodium hydroxide and 24.6 g (1.8 mol., 1.6 eq). The suspension was refluxed for 30′ before addition of 24.5 ml (2.3 mol., 2 equiv.) of benzyl chloride. The mixture was refluxed overnight before cooled to room temperature and extracted with 3×160 ml of diethyl ether. The organic solution was dried over sodium sulphate, and evaporated. The residue was distilled Kugel Rohr (100° C., 1 mm Hg). The suspension was refluxed for 30′ The mixture was refluxed overnight extracted with 3×160 ml of diethyl ether The organic solution was dried over sodium sulphate evaporated The residue was distilled Kugel Rohr (100° C., 1 mm Hg)

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

Procedure: Dibenzyl-[2-(3-benzyloxy-propoxy)-ethyl]-amine (860 mg) was prepared by following General Procedure W starting from toluene-4-sulfonic acid 3-benzyloxy-propyl ester (1.33 g), N,N-dibenzyl-2-aminoethanol (1.0 g), 50% aqueous sodium hydroxide solution (1.66 g in 1.66 mL of water), and tetrabutylammonium hydrogen sulfate (141 mg).

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

Procedure: Dibenzyl-[2-(3-benzyloxy-propoxy)-ethyl]-amine (860 mg) was prepared by following General Procedure W starting from toluene-4-sulfonic acid 3-benzyloxy-propyl ester (1.33 g), N,N-dibenzyl-2-aminoethanol (1.0 g), 50% aqueous sodium hydroxide solution (1.66 g in 1.66 mL of water), and tetrabutylammonium hydrogen sulfate (141 mg).

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

Procedure: To N,N-dibenzyl-2-aminoethanol (80.68 g) were added cyclohexane (500 ml) and DMF (12.9 ml), and thereto was added dropwise thionyl bromide (83.4 g). The mixture was stirred for 15 hours, and to the reaction solution was added an saturated aqueous sodium hydrogen carbonate solution in an ice-bath, and the mixture was extracted with ethyl acetate. The organic layer was washed with water (three times) and saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound (72.1 g). the mixture was extracted with ethyl acetate The organic layer was washed with water (three times) and saturated aqueous sodium chloride solution dried over sodium sulfate filtered concentrated under reduced pressure

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.5 gram of dibenzylamine (2.5 mmol), 0.446 gram of ethylenecarbonate (5 mmol) and 0.215 gram of tetraethylammoniumiodide (083 mmol) were mixed together at room temperature. The solid mixture was then heated at 140° C. and the resulting suspension was stirred at this temperature for 26 hours. The reaction mixture was diluted with ethyl acetate and extracted with 10 mL of a 0.5M solution of sodium hydroxide. The aqueous phase was washed with ethyl acetate and the combined organic phases were washed twice with brine. The organic phase was dried on magnesium sulfate, filtered, concentrated under reduced pressure and purified by flash chromatography on silica gel (eluant: ethylacetate/hexane 1/2) to afford 0.5 gram of N,N-dibenzyl-2-aminoethanol (yield: 83%) as an oil. extracted with 10 mL of a 0.5M solution of sodium hydroxide The aqueous phase was washed with ethyl acetate the combined organic phases were washed twice with brine The organic phase was dried on magnesium sulfate filtered concentrated under reduced pressure purified by flash chromatography on silica gel (eluant: ethylacetate/hexane 1/2)

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

Procedure: To N,N-dibenzyl-2-aminoethanol (18.47 g) was added hexane (150 ml) and DMF (0.3 ml), and thereto was added dropwise thionyl bromide (15.91 g) at 0° C. The mixture was stirred for 15 hours, and to the reaction solution was added a saturated aqueous sodium hydrogen carbonate solution in an ice-bath, and the mixture was extracted with ethyl acetate. The organic layer was washed with water (×2) and a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (the developing solvent: hexane) to give the title compound (12.80 g). the mixture was extracted with ethyl acetate The organic layer was washed with water (×2) a saturated aqueous sodium chloride solution, dried over sodium sulfate filtered concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (the developing solvent

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

Procedure: Tert-butyl 3-chloro-6-hydroxyindazole-1-carboxylate (4.3611 g) which can be prepared according to the method described in Reference example 39, etc. and 2-(dibenzylamino)ethanol (4.1529 g; manufactured by Tokyo Chemical Industry Co., Ltd.) were dissolved in dehydrated THF (100 mL), added with triphenylphosphine (7.9370 g; manufactured by Kanto Chemical Co., Inc.) and TMAD (5.2270 g; manufactured by Masuda Chemical Industries Co., Ltd.), and then stirred overnight at room temperature. The reaction solution was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in toluene, and the solvent was evaporated under reduced pressure. The resulting residue was purified by column chromatography (“COLUMN-D”; n-hexane:ethyl acetate=90:10→75:25) to obtain the title compound (7.1028 g). The reaction solution was filtered the filtrate was concentrated under reduced pressure The resulting residue was dissolved in toluene the solvent was evaporated under reduced pressure The resulting residue was purified by column chromatography (“COLUMN-D”; n-hexane:ethyl acetate=90:10→75:25)

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.5 gram of dibenzylamine (2.5 mmol), 0.446 gram of ethylenecarbonate (5 mmol) and 0.215 gram of tetraethylammoniumiodide (083 mmol) were mixed together at room temperature. The solid mixture was then heated at 140° C. and the resulting suspension was stirred at this temperature for 26 hours. The reaction mixture was diluted with ethyl acetate and extracted with 10 mL of a 0.5M solution of sodium hydroxide. The aqueous phase was washed with ethyl acetate and the combined organic phases were washed twice with brine. The organic phase was dried on magnesium sulfate, filtered, concentrated under reduced pressure and purified by flash chromatography on silica gel (eluant: ethylacetate/hexane 1/2) to afford 0.5 gram of N,N-dibenzyl-2-aminoethanol (yield: 83%) as an oil. extracted with 10 mL of a 0.5M solution of sodium hydroxide The aqueous phase was washed with ethyl acetate the combined organic phases were washed twice with brine The organic phase was dried on magnesium sulfate filtered concentrated under reduced pressure purified by flash chromatography on silica gel (eluant: ethylacetate/hexane 1/2)

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

Procedure: To a vigorously stirred solution of 6.7 ml (1.12 mol, 1 equiv.) ethanolamine in 120 ml of (1/1) MeOH/H2O were added 7.2 g (1.8 mol, 1.6 equiv.) of sodium hydroxide and 24.6 g (1.8 mol., 1.6 eq). The suspension was refluxed for 30′ before addition of 24.5 ml (2.3 mol., 2 equiv.) of benzyl chloride. The mixture was refluxed overnight before cooled to room temperature and extracted with 3×160 ml of diethyl ether. The organic solution was dried over sodium sulphate, and evaporated. The residue was distilled Kugel Rohr (100° C., 1 mm Hg). The suspension was refluxed for 30′ The mixture was refluxed overnight extracted with 3×160 ml of diethyl ether The organic solution was dried over sodium sulphate evaporated The residue was distilled Kugel Rohr (100° C., 1 mm Hg)