Hydrochloric Acid → N,N'-Dicyclohexylurea

HRID 2418665Notes

Reaction equation

HRID 2418665 reaction equation
Cl.N1C=CC=CC=1.FC(F)(F)C(O)=[O:11].[CH:15]1([N:21]=[C:22]=[N:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1>CS(C)=O>[CH:24]1([NH:23][C:22]([NH:21][CH:15]2[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]2)=[O:11])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 6422Trifluoroacetic acidHCID 10868Dicyclohexylcarbodiimide

Product 1

HCID 4277N,N'-Dicyclohexylurea

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

The product (the hydrochloride) (490 mg) obtained in the above procedure (d) of this Example was dissolved in 2.5 ml of anhydrous dimethylsulfoxide (DMSO) (serving as an oxidation reagent and also serving as the reaction medium), to which were then added 0.17 ml of pyridine and 0.08 ml of trifluoroacetic acid. The solution obtained was admixed with a solution of 600 mg of dicyclohexylcarbodiimide in 3 ml of anhydrous DMSO, followed by agitating the resultant admixture for 2 hours at ambient temperature (for effecting the oxidation reaction of the hydroxymethyl group). The solid as formed (comprising N,N'-dicyclohexyl urea) was removed from the reaction solution by filtration and the filtrate was well mixed with ethyl ether (about 20 ml) under shaking. This mixture obtained was left and so separated into the upper layer and the lower layer. The lower liquid layer was removed by decantation and then well washed with ethyl ether by agitating the admixture of said lower liquid layer and the ethyl ether. This admixture was allowed to stand so that it was separated into the upper phase and the lower phase. This lower liquid phase was concentrated, and the residue was taken up into about 40 ml of chloroform and the resultant solution in chloroform was washed with saturated aqueous sodium chloride (about 10 ml), and the solution phase in chloroform was separated from the aqueous phase, dried over anhydrous sodium sulfate and concentrated to dryness to leave a brown colored solid. This solid (485 mg) was dissolved in a mixture (20 ml) of concentrated aqueous ammonia and methanol (1:14) and the resultant mixture was allowed to stand for 3 hours at ambient temperature (for effecting the reaction for removal of the acetyl groups). The reaction solution was concentrated to dryness and the residue (370 mg) was taken up into water (2 ml). The solution obtained was filtered to remove the insoluble matters (about 40 mg, comprising N,N'-dicyclohexyl urea) therefrom. The filtrate was subjected to a column chromatography on Dowex 1×2 resin (30 ml, 200~400 meshes, Cl- form) using water as the development solvent. The eluate from the resin column was collected in 5 ml-fractions and the fractions Nos. 4 to 8 containing the above titled compound (which gave a single spot at Rf 0.6 on a cellulose thin layer chromatography developed with butanol-pyridine-water-acetic acid (6:4:3:1)) were combined together, neutralized by addition of 0.1 N hydrochloric acid and then concentrated to a small volume. The concentrated solution obtained was adjusted to a pH of about 4 by addition of 0.1 N hydrochloric acid and then admixed with a volume of acetone to deposit a solid. The solid obtained was well washed with acetone to afford 84 mg of hydrochloride of the title compound. Yield 21%. [α]D28 -64° (c 1, H2O).

Workup

  1. customThe solution obtained
  2. customthe oxidation reaction of the hydroxymethyl group)

Sources & evidence

ORD record
ord-305c216d4123424aa9168a9bacba3260
Source dataset
uspto-grants-1984_09
Patent number
US04473557

Reaction notes

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