1-amino-3-phenoxypropan-2-ol;hydrochloride

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

Procedure: 1-Succinimido-3-phenoxy-2-propanol (16 gm, 0.06 mole) was dissolved in 100 mL conc. HCl and 100 mL ethanol and heated to reflux for 6 hours. After the reaction, the mixture was evaporated to a white residue which was thentaken up in 25 mL water and washed with 3×50 mL ether. The aqueous phase was then evaporated and the white-residue recrystallized from ethanol to provide 8.3 gm (69%) of white crystals: mp 226°-228°. The NMR spectrum was consistent with the assignedstructure and the elemental analysis was consistent with the molecular formula C9H14NO2Cl. to reflux for 6 hours After the reaction the mixture was evaporated to a white residue which washed with 3×50 mL ether The aqueous phase was then evaporated the white-residue recrystallized from ethanol

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

Procedure: A solution of 1-amino-3-phenoxypropan-2-ol hydrochloride (7.9 g, 38.8 mmol) and 1-(2-chloroacetyl)pyrrolidine-2-carbonitrile (6.1 g, 35.3 mmol) in DCM (250 mL) was added triethylamine (15 mL, 106 mmol). The mixture was stirred at room temperature overnight. After the TLC showed that the reaction was complete, the mixture was washed by brine. The aqueous solution was extracted with dichloromethane (DCM) (3×100 mL) and the combined DCM solution was concentrated to give a crude product, which was purified by column chromatography to give 3.5 g of 1-(2-(2-hydroxy-3-phenoxypropylamino)acetyl)pyrrolidine-2-carbonitrile (as shown at 6). Yield was 33.6%. the mixture was washed by brine The aqueous solution was extracted with dichloromethane (DCM) (3×100 mL) the combined DCM solution was concentrated to give a crude product, which was purified by column chromatography

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

Procedure: A solution of 1-amino-3-phenoxypropan-2-ol hydrochloride (7.9 g, 38.8 mmol) and 1-(2-chloroacetyl)pyrrolidine-2-carbonitrile (6.1 g, 35.3 mmol) in DCM (250 mL) was added triethylamine (15 mL, 106 mmol). The mixture was stirred at room temperature overnight. After the TLC showed that the reaction was complete, the mixture was washed by brine. The aqueous solution was extracted with dichloromethane (DCM) (3×100 mL) and the combined DCM solution was concentrated to give a crude product, which was purified by column chromatography to give 3.5 g of 1-(2-(2-hydroxy-3-phenoxypropylamino)acetyl)pyrrolidine-2-carbonitrile (as shown at 6). Yield was 33.6%. the mixture was washed by brine The aqueous solution was extracted with dichloromethane (DCM) (3×100 mL) the combined DCM solution was concentrated to give a crude product, which was purified by column chromatography

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

Procedure: A solution of 1-(2-hydroxy-3-phenoxypropyl)pyrrolidine-2,5-dione (3.5 g, 13.1 mmol) (as shown at 3 above) in HCl (12N, 20 mL) and ethanol (20 mL) was heated to reflux for 6 hours. After thin layer chromatography (TLC) showed the reaction was complete, the mixture was concentrated in vacuum to give a white residue, which was taken up in water (20 mL) and washed with ether (3*50 mL). The aqueous phase was concentrated to give crude product, which was crystallized from methanol to give 2.9 g of 1-amino-3-phenoxypropan-2-ol hydrochloride (as shown at 4). to reflux for 6 hours the mixture was concentrated in vacuum to give a white residue, which washed with ether (3*50 mL) The aqueous phase was concentrated to give crude product, which was crystallized from methanol

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

Procedure: 1-Succinimido-3-phenoxy-2-propanol (16 gm, 0.06 mole) was dissolved in 100 mL conc. HCl and 100 mL ethanol and heated to reflux for 6 hours. After the reaction, the mixture was evaporated to a white residue which was thentaken up in 25 mL water and washed with 3×50 mL ether. The aqueous phase was then evaporated and the white-residue recrystallized from ethanol to provide 8.3 gm (69%) of white crystals: mp 226°-228°. The NMR spectrum was consistent with the assignedstructure and the elemental analysis was consistent with the molecular formula C9H14NO2Cl. to reflux for 6 hours After the reaction the mixture was evaporated to a white residue which washed with 3×50 mL ether The aqueous phase was then evaporated the white-residue recrystallized from ethanol

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

Procedure: A solution of 1-amino-3-phenoxypropan-2-ol hydrochloride (7.9 g, 38.8 mmol) and 1-(2-chloroacetyl)pyrrolidine-2-carbonitrile (6.1 g, 35.3 mmol) in DCM (250 mL) was added triethylamine (15 mL, 106 mmol). The mixture was stirred at room temperature overnight. After the TLC showed that the reaction was complete, the mixture was washed by brine. The aqueous solution was extracted with dichloromethane (DCM) (3×100 mL) and the combined DCM solution was concentrated to give a crude product, which was purified by column chromatography to give 3.5 g of 1-(2-(2-hydroxy-3-phenoxypropylamino)acetyl)pyrrolidine-2-carbonitrile (as shown at 6). Yield was 33.6%. the mixture was washed by brine The aqueous solution was extracted with dichloromethane (DCM) (3×100 mL) the combined DCM solution was concentrated to give a crude product, which was purified by column chromatography

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

Procedure: A solution of 1-(2-hydroxy-3-phenoxypropyl)pyrrolidine-2,5-dione (3.5 g, 13.1 mmol) (as shown at 3 above) in HCl (12N, 20 mL) and ethanol (20 mL) was heated to reflux for 6 hours. After thin layer chromatography (TLC) showed the reaction was complete, the mixture was concentrated in vacuum to give a white residue, which was taken up in water (20 mL) and washed with ether (3*50 mL). The aqueous phase was concentrated to give crude product, which was crystallized from methanol to give 2.9 g of 1-amino-3-phenoxypropan-2-ol hydrochloride (as shown at 4). to reflux for 6 hours the mixture was concentrated in vacuum to give a white residue, which washed with ether (3*50 mL) The aqueous phase was concentrated to give crude product, which was crystallized from methanol