Reductive Alkylation of aminoethanolReductive Alkylation of aminoethanol
SyntheticPage 593
Published Apr 23, 2013
A 1-liter 3 necked round bottomed flask containing a mechanical stirrer, thermometer pocket, water/oil heating bath was assembled under an atmosphere of dinitrogen. Ethanol (400 mL) and aminoethanol (61 g, 1 mol) were charged. The reaction temperature was raised to about 45 oC. To this solution, benzaldehyde (106 g, 1 mol) was added over a period of 30 min. The reaction mass was further refluxed for 3 h. At this point, TLC of the reaction mixture shows almost conversion of benzaldehyde to corresponding imine (2:8, ethylacetate: hexane). The reaction mass was cooled to about 35-40oC and a solution of sodium borohydride (19 g, 0.5 mol) in 40 mL aqueous sodium hydroxide solution (400 mg NaOH in 40 ml water) was added over a period of 90 min keeping the reaction temperature below 40oC. The reaction mixture was stirred at the same temperature for 4 h. The ethanol was distilled off almost completely under vacuum. The reaction mass was added to about 250 mL water containing ammonium chloride (50 g) and extracted with dichloromethane at least 4 times (500 mL each). The dichloromethane extracts were washed with sodium carbonate solution (500 mL, 10%), dried with sodium sulfate and evaporated thoroughly to leave an oily mass (140 g, 92.7%) about 95% pure by GC. This can be further purified by vacuum distillation (one can get about 75% main fraction). Alternatively, this can be purified by converting to maleate salt - please find details below. The maleate can be bascified and extracted in dichloromethane.
Purification of the product by converting into Maleate salt:
The crude product from above reaction (~ 140 g , 0.92 mol) was dissolved in ethyl acetate (800 mL ) by warming to about 50 oC. Maleic acid (107 g, 0.92 mol) was added all at once and the mixture was stirred for 15 min then cooled to 20 oC. The almost white solid was filtered off (~ 325 g, wet) and washed with ethyl acetate (200 mL). The solid thus isolated was added to 5 l flask containing water ( 900 mL) and dichloromethane (750 mL) under stirring. The mixture was chilled to 10oC and treated with aqueous ammonia (~200 mL) . The dichloromethane layer thus obtained was separated and the water layer extracted with further dichloromethane (750 mL). The combined organic extracts were washed with water ( 500 mL) and dried over sodium sulphate ( 200g). Finally, dichloromethane was removed under reduced pressure to get about 110-113 g (~ 75%) pure product.