Allylamine → 1-Cyclohexene-1-carboxylic acid, 3-(1-ethylpropoxy)-4-hydroxy-5-(2-propen-1-ylamino)-, ethyl ester, (3R,4S,5R)-

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Reaction Conditions

Reaction Steps

In a 2.5 l 4-necked round bottom flask equipped with a reflux condenser, a thermometer, a mechanical stirrer and an inert gas supply 254.3 g (1.0 mol) of (1S,5R,6S)-5-(1-ethyl-propoxy)-7-oxa-bicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester were dissolved under argon with stirring in 900 ml tert.-butyl methyl ether and 100 ml acetonitrile whereby the temperature dropped to about 10° C. To the clear, yellowish solution 51.7 g (0.2 mol) of magnesium bromide diethyl etherate were added followed by 150 ml (2.0 mol) of allylamine whereby the temperature rose to about 20° C. The yellow suspension was heated to 55° C. whereby complete dissolution occurred after about 1.5 h. The clear yellow solution was refluxed for 15 h. The yellowish, turbid solution was cooled to about 30° C. and stirred vigorously with 1000 ml of 1M aqueous ammonium sulfate for 15 min whereby a clear two-phase mixture evolved after initial cloudiness. The organic phase was separated, filtered and evaporated in a rotary evaporator at 48° C./340 mbar to a volume of about 580 ml. The solid particles were filtered and the brown solution was evaporated at 48° C./340 to 15 mbar for 2 h to yield as the crude product 312.8 g (97%) of (3R,4S,5R)-5-allylamino-3-(1-ethyl-propoxy)-4-hydroxy-cyclohex-1-enecarboxylic acid ethyl ester as a brown-yellow oil containing about 7.0% of the 4-allylamino-5-hydroxy isomer.

Provenance & Evidence