(2R)-1-(benzylamino)propan-2-ol

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

Procedure: Stir a mixture of 3.5 g (21.2 mmol) (2R)-1-(benzylamino)propan-2-ol [F. L. Delft, Synthesis 1997, 4, 450-454], 1.85 ml (2.0 g, 23.3 mmol) of a 35% aqueous formaldehyde solution and 3.6 ml (4.4 g, 95.3 mmol) formic acid for 16 h under reflux. After cooling to room temperature, first neutralize with 45% sodium hydroxide solution and then adjust to a pH value of 9. Extract with ethyl acetate. Wash the organic phase three times with 10 ml water each time, dry over sodium sulphate and filter. Concentrate the filtrate by vacuum evaporation, and dry. 3.08 g (78% of theor.) of the desired product is obtained. under reflux Extract with ethyl acetate Wash the organic phase three times with 10 ml water each time dry over sodium sulphate filter Concentrate the filtrate by vacuum evaporation dry

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

Procedure: 2,6-Dibromo-3-nitropyridine (2.59 g, 9.20 mmol) and triethylamine (2.70 mL, 19.37 mmol) were added to a solution of (R)-1-(benzylamino)propan-2-ol (1.6 g, 9.68 mmol) in ethanol (35 mL). The solution was stirred at rt for 17 h and then concentrated under reduced pressure. The residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution (25 mL). The layers were separated, and the organic layer was washed with 5% aqueous sodium chloride solution (25 mL). The ethyl acetate layer was concentrated under reduced pressure to afford an orange syrup. The crude product was purified by column chromatography on silica gel (eluting with 5:1 hexanes-ethyl acetate followed by 3:1 hexanes-ethyl acetate) to afford (R)-1-(benzyl(6-bromo-3-nitropyridin-2-yl)amino)propan-2-ol (3.01 g, 85%) as a bright yellow syrup. MS (ESI, pos. ion) m/z 388, 390 [M+Na]+. concentrated under reduced pressure The residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution (25 mL) The layers were separated the organic layer was washed with 5% aqueous sodium chloride solution (25 mL) The ethyl acetate layer was concentrated under reduced pressure to afford an orange syrup The crude product was purified by column chromatography on silica gel (eluting with 5:1 hexanes-ethyl acetate followed by 3:1 hexanes-ethyl acetate)

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

Procedure: A 100-mL round bottomed flask equipped with a magnetic stir bar was charged with (R)-1-aminopropan-2-ol (1.0 g, 13.31 mmol), dichloromethane (25 mL), benzaldehyde (1.349 mL, 13.31 mmol), and magnesium sulfate (4.81 g, 39.9 mmol), and the mixture stirred at rt for 24 h. The slurry was filtered through a medium frit Buchner funnel and the solids were washed with additional dichloromethane. The filtrate was concentrated to a colorless syrup. The crude imine (2.171 g, 13.3 mmol) was dissolved in methanol (30 mL) and treated with sodium borohydride (0.503 g, 13.30 mmol) in two portions (0.200 g then 0.303 g 5 min later) at rt. The solution was stirred at rt for 4 h and then concentrated under reduced pressure. The residue was dissolved in 1 N aqueous hydrogen chloride solution (40 mL). This aqueous solution was washed with ethyl acetate (2×40 mL). The aqueous layer was made basic by the addition of 10 N aqueous sodium hydroxide solution (8 mL) and extracted with dichloromethane. The dichloromethane layer was washed with 5% aqueous sodium chloride solution (20 mL) and concentrated under reduced pressure to afford (R)-1-(benzylamino)propan-2-ol (1.61 g, 73%) as a colorless syrup. MS (ESI, pos. ion) m/z 166 [M+1]+. A 100-mL round bottomed flask equipped with a magnetic stir bar The slurry was filtered through a medium frit Buchner funnel the solids were washed with additional dichloromethane The filtrate was concentrated to a colorless syrup 0.303 g 5 min at rt The solution was stirred at rt for 4 h concentrated under reduced pressure The residue was dissolved in 1 N aqueous hydrogen chloride solution (40 mL) This aqueous solution was washed with ethyl acetate (2×40 mL) The aqueous layer was made basic by the addition of 10 N aqueous sodium hydroxide solution (8 mL) extracted with dichloromethane The dichloromethane layer was washed with 5% aqueous sodium chloride solution (20 mL) concentrated under reduced pressure