Hexamethylenetetramine → ethyl 2-[(1R)-1-(2-tert-butoxy-2-oxoethyl)-4-cyclohexylbutyl]-1,3-oxazole-4-carboxylate

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Reaction Steps

A suspension of CuBr2 (20.88 g, 93.5 mmol) and HMTA (13.1 g, 93.5 mmol) in degassed DCM (250 ml) was treated with DBU (14.0 ml, 93.5 mmol) and the dark solution formed was stirred in a water bath for 5 minutes. A solution of ethyl (4S)-2-[(1R)-1-(2-tert-butoxy-2-oxoethyl)-4-cyclohexylbutyl]-4,5-dihydro-1,3-oxazole-4-carboxylate (preparation 152) (9.24 g, 23.4 mmol) in degassed DCM (30 ml) was added dropwise to the reaction mixture and stirred at room temperature for a further 3 hours. The solvent was removed under reduced pressure. The resdue was dissolved in EtOAc and washed with a 1:1 solution of NH3(aq):NH4Cl. The aqueous extract was washed with EtOAc (2×380 ml). The combined organic extracts were washed with 2M HCl (500 ml), sat. NaHCO3 (500 mL) and brine (500 ml). The organic extracts were dried over anhydrous MgSO4 and filtered. The solvent was removed under reduced pressure. The crude material was purified on a silica column eluting with a solvent gradient of EtOAc:pentane (0:100) gradually changing to (25:75) to afford the title compound as colourless oil which formed needles on standing (7.39 g, 80%).

Provenance & Evidence