Diethyl Ether → N,N'-Dicyclohexylurea

HRID 436258Notes

Reaction equation

HRID 436258 reaction equation
C1[C@H](N)[C@@H]([O:8][C@H]2O[C@H](CN)[C@@H](O)[C@H](O)[C@H]2N)[C@H](O[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)[C@@H](O)[C@@H]1N.FC(F)(F)C(O)=O.C(OCC)C.[CH:44]1([N:50]=[C:51]=[N:52][CH:53]2[CH2:58][CH2:57][CH2:56][CH2:55][CH2:54]2)[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]1>C(O)(=O)C>[CH:53]1([N:52]=[C:51]=[N:50][CH:44]2[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]2)[CH2:54][CH2:55][CH2:56][CH2:57][CH2:58]1.[C:51]([NH:50][CH:44]1[CH2:45][CH2:46][CH2:47][CH2:48][CH2:49]1)([NH:52][CH:53]1[CH2:58][CH2:57][CH2:56][CH2:55][CH2:54]1)=[O:8]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 6422Trifluoroacetic acidHCID 10868DicyclohexylcarbodiimideHCID 33042Ribostamycin

Product 2

HCID 4277N,N'-DicyclohexylureaHCID 10868Dicyclohexylcarbodiimide

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

30 g. of ribostamycin (the free base form) was added to 127 ml. of trifluoroacetic acid under ice-cooling and stirring, and the mixture was allowed to stand at ambient temperature overnight. The resulting solution of amber color was admixed with 400 ml of ethyl ether, and the admixture was cooled to precipitate 69 g of a salt of ribostamycin with trifluoroacetic acid which was then removed by filtration. A 20 g. portion of this ribostamycin trifluoroacetate was taken and then dissolved in 250 ml of tetrahydrofuran together with 16.4 g. of (S)-α-hydroxy-γ-N-phthalimido-n-butyric acid of the formula ##STR25## The solution was cooled with ice. A solution of 36.4 g of dicylcohexylcarbodiimide in 146 ml of tetrahydrofuran was prepared and cooled with ice. Both the solutions was combined together under ice-cooling and stirring. The combined solutions were agitated at ambient temperature for 2-3 hours and admixed with 8 ml of glacial acetic acid to decompose the excess of dicyclohexylcarbodiimide. 3286 mg of dicyclohexylurea produced was deposited and filtered off. The filtrate was concentrated to dryness, giving 43 g of a pale yellow colored solid comprising mixed trifluoroacetic acid salts of O-((S)-α-hydroxy-γ-N-phthalimido-n-butyryl)-ribostamycins.

Workup

  1. temperaturethe admixture was cooled
  2. customto precipitate 69 g of a salt of ribostamycin with trifluoroacetic acid which
  3. customwas then removed by filtration
  4. dissolutiondissolved in 250 ml of tetrahydrofuran together with 16.4 g
  5. temperatureof (S)-α-hydroxy-γ-N-phthalimido-n-butyric acid of the formula ##STR25## The solution was cooled with ice
  6. temperaturecooled with ice
  7. temperaturecooling
  8. stirringstirring
  9. stirringThe combined solutions were agitated at ambient temperature for 2-3 hours

Sources & evidence

ORD record
ord-cc3eb347148449708e50abae7383274f
Source dataset
uspto-grants-1977_02
Patent number
US04008218

Reaction notes

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