Phenylacetic Acid → N,N'-Dicyclohexylurea

HRID 2308370Notes

Reaction equation

HRID 2308370 reaction equation
S(=O)(=O)(O)O.C1(CC(O)=[O:14])C=CC=CC=1.[CH:16]1([N:22]=[C:23]=[N:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1>N1C=CC=CC=1>[CH:25]1([NH:24][C:23]([NH:22][CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]2)=[O:14])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

5

Reactant 3

HCID 999Phenylacetic AcidHCID 1118Sulfuric AcidHCID 10868Dicyclohexylcarbodiimide

Product 1

HCID 4277N,N'-Dicyclohexylurea

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

A freshly prepared mixture of 30 mg of concentrated sulfuric acid in 2.5 ml of absolute pyridine (suspension of pyridinium sulfate) is added, at 20° C. and while stirring, to a solution of 1.1 g (0.0025 mol) of prednisolone 17-n-butyrate and 1.2 g (0.0088 mol) of phenylacetic acid (dried at about 50 to 60° C. for 5 hours in vacuo over P2O5) in 6 ml of absolute pyridine. After stirring for 15 minutes, 720 mg (0.0035 mol) of N,N′-dicyclohexylcarbodiimide are added. A crystalline precipitate of the N,N′-dicyclohexylurea which has been formed soon separates out from the initially clear solution. The mixture is stirred until starting material can no longer be detected by TLC and the reaction product is detectable at RF=0.8 (as a rule, a reaction time of 16 hours; a longer reaction time, e.g. standing or stirring over the weekend, does not impair the reaction result). After this, 0.3 ml of acetic acid or acetic anhydride is added and the mixture is left to stand for a further 1 hour at 20° C. and then 24 to 48 hours in a deep-freeze (about −15° C.). The precipitated N,N′-dicyclohexylurea is filtered off and washed with cold pyridine (about −15° C.), and the filtrate is stirred into about 400 ml of a quarter-saturated aqueous solution of sodium chloride; about 5 ml of ethanol are added and the oily-crystalline precipitate is filtered off, washed several times with water and then taken up in about 20 ml of methylene chloride. After drying with sodium sulfate, the solvent is distilled off and the residue is crystallized by adding diethyl ether or diisopropyl ether. 1.1 g of prednisolone 17-n-butyrate 21-phenyl acetate with a melting point of about 106° C. are obtained and can be recrystallized from tert-butanol/diethyl ether.

Workup

  1. additionis added, at 20° C.

Sources & evidence

ORD record
ord-02d090f7101c408db8cd23a08bca013c
Source dataset
uspto-grants-2004_12
Patent number
US06835724B2

Reaction notes

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