Ethylamine → 5-((tert-butyldiphenylsilyloxy)methyl)-6-((2R,6S)-2,6-dimethylmorpholino)-N-ethyl-7-fluorobenzo[d]isoxazole-3-carboxamide

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Reaction Steps

Under a nitrogen atmosphere, trimethylaluminum (2M in toluene, 1206 μl, 2.41 mmol) was slowly added (gas evolution) to an ice cooled solution of ethylamine (2M in THF) (1206 μl, 2.41 mmol) in 7 ml of toluene. The reaction was allowed to warm to room temperature and stirred for 2 hours. Ethyl 5-((tert-butyldiphenylsilyloxy)methyl)-6-((2R,6S)-2,6-dimethylmorpholino)-7-fluorobenzo[d]isoxazole-3-carboxylate, (Intermediate 204, 190 mg, 0.32 mmol) was added as a solution in toluene (3 ml). The reaction was stirred at 45° C. for 18 hours. The reaction was quenched drop wise (vigorous gas evolution) with 2 ml of 1N HCl. The crude reaction was filtered to remove solids, diluted with water and extracted twice with ethyl acetate. The organic layers were combined, washed twice with brine, dried over MgSO4 and concentrated to give an oil. The oil was purified by silica gel column chromatorgraphy using a gradient of hexanes to ethyl acetate. Fractions were combined and concentrated to give the title compound. (170 mg, 0.288 mmol, 90%).

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