Cortisol → N,N'-Dicyclohexylurea

Participants

Reaction Steps

To a solution of hydrocortisone (5 g, 0.014 mole) and N,N-di-n-propylsuccinamic acid (2.78 g, 0.014 mole) in 25 ml pyridine at room temperature was added dicyclohexylcarbodiimide (2.85 g, 0.014 mole). After the reaction was stirred 10 minutes, 25 ml dichloromethane was added to it to keep the suspension which had formed sufficiently fluid for stirring. After the reaction was stirred overnight, it was filtered. The residue was washed twice with CH2Cl2 and dried in the air to give 2.46 g (91% yield) dicyclohexylurea. The filtrate was concentrated in vacuo to a residue which was dissolved in 25 ml hot THF. After the THF solution was filtered while hot, the resulting filtrate was diluted to 150 ml with Et2O. The product crystallized overnight and was filtered and dried to give 3.49 g of light brown crystals, which a preliminary NMR showed to be contaminated with solvent. The crystals were dried in vacuo (50° C., 2 hours) to give 2.81 g (37% yield) of the desired product: mp 157°-162° C.; NMR (CDCl3) δ5.64 (s, 1, O=C-CH=), 4.98 (m, 2, O=C-CH2O), 4.46 (m, 1, CHOH), 3.8-4.2 (m, 2, OH), 3.24 (t, 4, J=7 Hz, N CH2), 2.70 (s, 4, OCCH2CH2CO), 1.46 (s, 3, C-CH3), 0.96 (s, 3, C-CH3), 0.94 (m, 6, N(CH2CH2CH3)2), 2.9-0.8 (m, 21, CH, CH2); TLC (silica gel, 10% MeOH/Et2O) Rf 0.56; [α]25D=+127° (C=0.5, dioxane); IR (KBr) 3400 cm-1 (s) (OH), 1730, 1710, 1640 and 1610 cm-1 (s) (C=O).

Provenance & Evidence