(1R,2S)-2-amino-1-phenylpropan-1-ol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: As shown in the scheme above, (1R, 2S)-(−)-norephedrine is reacted with an optionally substituted benzaldehyde by refluxing in ethanol, and reducing the product of that reaction with sodium borohydride at ambient temperature to produce the desired norephedrine derivative compound.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A process for the preparation of [R-(R*,S*)]-β-methyl-α-phenyl-1-pyrrolidineethanol hydrochloride or its enantiomer, ##STR53## comprising the steps of: (a) refluxing (1R,2S)-(-)-norephedrine or its enantiomer, ##STR54## with 1,4-dibromobutane in the presence of a base, sodium bicarbonate and a solvent, toluene, at a reaction temperature of about 100° to about 120° C. for reaction time of about 12 to about 24 hours, while removing the water formed to give a toluene solution of crude [R-(R*,S*)]-β-methyl-α-phenyl-1-pyrrolidineethanol or its enantiomer; while removing the water formed

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A process for the preparation of [R-(R*,S*)]-β-methyl-α-phenyl-1-pyrrolidineethanol hydrochloride or its enantiomer, ##STR12## comprising the steps of (a) refluxing (1R,2S)-(-)-norephedrine or its enantiomer, ##STR13## with 1,4-dibromobutane in the presence of a base, sodium bicarbonate and a solvent, toluene, at a reaction temperature of about 100° to about 120° C. for reaction time of about 12 to about 24 hours, while removing the water formed to give a toluene solution of crude [R-(R*,S*)]-β-methyl-α-phenyl-1-pyrrolidineethanol; while removing the water formed

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 61 grams of this salt were split in a manner analogous to that described in example 1. There were obtained 33 grams of L-3-formyl-2,2,5,5-tetramethyl-thiazolidine-4-carboxylic acid melting at 179° - 180°C.; [α]D20 - 54.4° as well as 26.5 grams of d-phenylpropanolamine.HCl melting point 173°C.; [α]D20 + 33°. From the mother liquor of the racemate splitting by evaporation to dryness and treatment with isopropanolic HCl there were obtained 28 grams (77%) of l-phenylpropanolamine.HCl, melting point 179°C.; [α]D20 - 31.4°. [α]D20 + 33° From the mother liquor of the racemate splitting by evaporation to dryness and treatment with isopropanolic HCl there

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 61 grams of this salt were split in a manner analogous to that described in example 1. There were obtained 33 grams of L-3-formyl-2,2,5,5-tetramethyl-thiazolidine-4-carboxylic acid melting at 179° - 180°C.; [α]D20 - 54.4° as well as 26.5 grams of d-phenylpropanolamine.HCl melting point 173°C.; [α]D20 + 33°. From the mother liquor of the racemate splitting by evaporation to dryness and treatment with isopropanolic HCl there were obtained 28 grams (77%) of l-phenylpropanolamine.HCl, melting point 179°C.; [α]D20 - 31.4°. [α]D20 + 33° From the mother liquor of the racemate splitting by evaporation to dryness and treatment with isopropanolic HCl there

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 200 ml of benzene, 43 g. (0.5 moles) of methyl acrylate and 76 g. of l-norephedrine are added to a 500 ml. three neck flask and refluxed overnight. To the solution is slowly added 15 g. (0.5 moles) of paraformaldehyde and the water removed using a Dean-Stark head. Concentrate the solution in vacuo on a steam bath and distill. The product boils at 137°-139° C./0.5 mm. The yield is 62 g.; n24 d=1.5155. three neck flask and refluxed overnight Concentrate the solution in vacuo on a steam bath distill

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 100 ml. of toluene, 43 g. (0.5 moles) of methyl acrylate and 76 g. (0.5 moles) of l-norephedrine are added to a 500 ml. three neck flask and stirred at room temperature for 24 hours. To the solution is added 50.4 g. (0.7 mole) of isobutyraldehyde and the mixture is heated to remove the water formed, by azeotropic distillation. When no more water can be removed, concentrate and distill. The oxazolidine proprionic acid methylester boils at 140°-160° C./0.5 mm. The yield is 129 g. (87%) n23 d =1.5020. To the solution is added 50.4 g to remove the water formed, by azeotropic distillation When no more water can be removed concentrate distill

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 100 ml. of toluene, 43 g. (0.5 moles) of methyl acrylate and 76 g. (0.5 moles) of l-norephedrine are added to a 500 ml. three neck flask and stirred at room temperature for 24 hours. To the solution is added 50.4 g. (0.7 mole) of isobutyraldehyde and the mixture is heated to remove the water formed, by azeotropic distillation. When no more water can be removed, concentrate and distill. The oxazolidine proprionic acid methylester boils at 140°-160° C./0.5 mm. The yield is 129 g. (87%) n23 d =1.5020. To the solution is added 50.4 g to remove the water formed, by azeotropic distillation When no more water can be removed concentrate distill

反応条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 5-iodo-1-isopropyl-1H-indazole (129c, 461 mg, 1.26 mmol), (1R,2S)-2-amino-1-phenylpropan-1-ol (286 mg, 1.89 mmol), copper (I) iodide (25 mg, 130 μmol), and cesium carbonate (1.45 g, 3.8 mmol) in butyronitrile (5 ml) was stirred at 125° C. for 2 h. Then the mixture was cooled to r.t., the inorganic material was removed by filtration and washed with ethyl acetate. The combined organic solutions were concentrated in vacuo, and the product purified by flash chromatography on silica gel (ethyl acetate/methanol). Yield 200 mg (51%) of a brown oil. Then the mixture was cooled to r.t. the inorganic material was removed by filtration washed with ethyl acetate The combined organic solutions were concentrated in vacuo the product purified by flash chromatography on silica gel (ethyl acetate/methanol)

反応条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 5-iodo-1-isopropyl-1H-indazole (129c, 461 mg, 1.26 mmol), (1R,2S)-2-amino-1-phenylpropan-1-ol (286 mg, 1.89 mmol), copper (I) iodide (25 mg, 130 μmol), and cesium carbonate (1.45 g, 3.8 mmol) in butyronitrile (5 ml) was stirred at 125° C. for 2 h. Then the mixture was cooled to r.t., the inorganic material was removed by filtration and washed with ethyl acetate. The combined organic solutions were concentrated in vacuo, and the product purified by flash chromatography on silica gel (ethyl acetate/methanol). Yield 200 mg (51%) of a brown oil. Then the mixture was cooled to r.t. the inorganic material was removed by filtration washed with ethyl acetate The combined organic solutions were concentrated in vacuo the product purified by flash chromatography on silica gel (ethyl acetate/methanol)

反応条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Iodo-1-pyridin-2-yl-1H-indazole (118b, 81 mg, 0.25 mmol), (1R,2S)-(−)-norephedrine (119 mg, 0.79 mmol) and butyronitrile (3 ml) were charged in a 7 ml vial. Copper(I) iodide (5.8 mg, 0.1 mol %) and cesium carbonate (261 mg, 0.8 mmol) were added, the vial was sealed and the solution was stirred (magnetic bar) at 125° C. for 2 h. Inorganic material was filtered off, and washed with ethyl acetate. The ethyl acetate phase was collected and concentrated and purified on silica with methanol:ethyl acetate 0:100 to 30:70 over 45 min. Pure fractions were pooled and concentrated to give 14 mg (16%) of 1-methyl-2-phenyl-2-(1-pyridin-2-yl-1H-indazol-5-yloxy)-ethylamine. the vial was sealed Inorganic material was filtered off washed with ethyl acetate The ethyl acetate phase was collected concentrated purified on silica with methanol:ethyl acetate 0:100 to 30:70 over 45 min concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (1R,2S)-Norephedrine (500 mg, 3.31 mmol), methyl-4-(5-iodoindazole-1-yl)-benzoate (1.28 g, 3.37 mmol), cesiumcarbonate (2.15 g, 6.61 mmol), copper (I)-iodide (314.9 mg, 1.65 mmol) and butyronitrile (2 mL) are stirred in a glass pressure tube at 120° C. for 20 h. The reaction mixture is filtered via a glass microfibre filter, the solvent evaporated and the residue purified by chromatography (silicagel, eluents: dichloromethane/methanol). 217.9 mg (16.4%) of the title compound are obtained. The reaction mixture is filtered via a glass microfibre filter the solvent evaporated the residue purified by chromatography (silicagel, eluents: dichloromethane/methanol)