Triethylamine → (1R,2S,5R)-5-Methyl-2-(propan-2-yl)cyclohexyl N-(2-{[(tert-butoxy)carbonyl]amino}-2-methylcyclopentyl)carbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-{[(tert-butoxy)carbonyl]amino}-2-methylcyclopentane-1-carboxylic acid (42.68 g, 175 mmol) and triethylamine (25.7 ml, 184 mmol) in toluene (250 ml) at room temperature was added {[azido(phenoxy)phosphoryl]oxy}benzene (CAS number 26386-88-9; 37.8 ml, 175 mmol) as a solution in toluene (100 ml). The reaction was heated to 60° C. for 2 hours, then (1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexan-1-ol (CAS number 2216-51-5; 14.25 g, 91 mmol) was added. The reaction was heated at 90° C. for 20 hours and then cooled to room temperature, quenched by the addition of water (50 ml) and diluted with ethyl acetate (200 ml). The organics were washed with a saturated solution of sodium bicarbonate (2×100 ml), brine (100 ml), dried over magnesium sulfate, filtered through a hydrophobic frit and concentrated in vacuo. The residue was purified by column chromatography (silica, petrol—10% ethyl acetate/petrol—20% ethyl acetate/petrol (step gradient)) to afford the title compound (a mixture of trans-amino compounds) which was taken on to next stage without further purification.

Provenance & Evidence