Réaction #55697

Équation de réaction

hydrocortisone

N,N-diethyl-3-oxaglutaramic acid

dicyclohexylcarbodiimide

→

dicyclohexylurea

Rendement 89.0%

Solvants

pyridine

Conditions de réaction

Traitement

1. 1
   workup.ADDITION25 ml CH2CH2 was added to it
2. 2
   Autrehad formed sufficiently fluid
3. 3
   workup.STIRRINGfor stirring
4. 4
   workup.STIRRINGThe reaction was stirred overnight at room temperature
5. 5
   Filtrationthen filtered
6. 6
   LavageThe residue was washed twice with CH2Cl2
7. 7
   Autredried

Mode opératoire

To a solution of hydrocortisone (5.12 g, 0.014 mole) and N,N-diethyl-3-oxaglutaramic acid (2.57 g, 0.015 mole) in 15 ml pyridine was added dicyclohexylcarbodiimide (3.06 g, 0.015 mole). After the reaction was stirred 10 minutes, 25 ml CH2CH2 was added to it to keep the suspension which had formed sufficiently fluid for stirring. The reaction was stirred overnight at room temperature then filtered. The residue was washed twice with CH2Cl2 and dried to give 2.6 g (89% yield) dicyclohexylurea. The filtrate was concentrated in vacuo to give a foam which was suspended in 20 ml hot dichloromethane and allowed to cool. The suspension was filtered and the filtrate was concentrated in vacuo to give a residue which was dissolved in 20 ml THF; the solution was then diluted to 100 ml with Et2O. Crystals formed overnight and were filtered to give 2.69 g of product which TLC showed to be contaminated with hydrocortisone. These crystals were in turn recrystallized from THF-Et2O (20:80). After 5 days, 2.14 g (29% yield) of light brown needles were filtered which were the etherate of the desired product: mp 95°-97.5° C., NMR (CDCl3) δ5.67 (s, 1, O=C--CH=), 5.07 (s, 2, O=C--CH2O--C=O), 4.48 (m, 3, CHOH,--OH), 4.35 (s, 2, --OCOCH2O--), 4.30 (s, 2, NCOCH2O--), 3.48 (q, 4, O(CH2CH3)2, J=5 Hz), 3.34 (m, 4, N(CH2CH3)2), 1.44 (s, 3, C--CH3), 1.18 (t, 6, O(CH2CH3)2, J=5 Hz), 0.93 (s, 3, C--CH3), 2.9-0.9 (m, 23, CH, CH2); IR (KBr) 3400 cm-1 (s) OH and 1730, 1710 and 1640 cm-1 (s) (C=O); TLC (silica gel, 10% MeOH/Et2O) Rf 0.36; [α]23D=+117° (C=0.5, dioxane).

Source