Diisopropylethylamine → tert-Butyl {(2S)-4-[1-(3,4-dichlorophenyl)ethyl]morpholin-2-yl}methylcarbamate

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Reaction Steps

tert-Butyl (2R)-morpholin-2-ylmethylcarbamate (2.00 g) in N,N-dimethylformamide (16 ml) was treated with N,N-diisopropylethylamine (1.6 ml) followed by 4-(1-bromoethyl)-1,2-dichlorobenzene (2.58 g). After stirring for five days at room temperature, further portions of 4-(1-bromoethyl)-1,2-dichlorobenzene (2.58 g) and N,N-diisopropylethylamine (1.6 ml) were added and stirring continued for 24 h at room temperature. The solution was treated with dichloromethane (70 ml) and saturated aqueous sodium hydrogen carbonate (30 ml) and the mixture shaken vigorously. The organic phase was separated and applied equally onto sulphonic acid ion exchange cartridges (5×10 g Isolute SCX, pre-treated with methanol). The cartridges were each eluted with methanol (one column volume) followed by 10% 0.880 ammonia in methanol (one column volume); evaporation in vacuo of the combined basic fractions gave the title compound as a clear colourless gum (3.22 g)

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