Dicyclohexylcarbodiimide → Naproxen Succinimide

HRID 1943980Notes

Reaction equation

[CH3:1][C@H:2]([C:15]([OH:17])=[O:16])[C:3]1[CH:4]=[CH:5][C:6]2[CH:7]=[C:8]([O:13][CH3:14])[CH:9]=[CH:10][C:11]=2[CH:12]=1.O[N:19]1[C:23](=[O:24])[CH2:22][CH2:21][C:20]1=[O:25].C1(N=C=NC2CCCCC2)CCCCC1>O1CCOCC1>[CH3:1][C@H:2]([C:15]([OH:17])=[O:16])[C:3]1[CH:4]=[CH:5][C:6]2[CH:7]=[C:8]([O:13][CH3:14])[CH:9]=[CH:10][C:11]=2[CH:12]=1.[C:20]1(=[O:25])[NH:19][C:23](=[O:24])[CH2:22][CH2:21]1

Participants

Conditions

Temperature: 4 °C

Procedure

To Naproxen (2.303 g, 10 mmol) in 5 mL of dioxane was added N-hydroxysuccinimide (1.16 g, 10 mmol) dissolved in 15 mL of dioxane and dicyclohexylcarbodiimide (2.27 g, 11 mmol) in 25 mL of dioxane. The reaction was stirred overnight and the insoluble dicyclohexylurea removed by filtration. The solvent was removed by rotary evaporation and the residue dissolved in 30-40 mL CH2Cl2. Approximately 10 mL hexane was added and the mixture was chilled to 4° C. for 2 hr. Additional hexane was added dropwise until small planar white crystals began to form and the solution was refrigerated overnight. The activated ester was harvested, washed with hexane and dried in vacuum (2.30 g, 70.0%)

Workup

customthe insoluble dicyclohexylurea removed by filtration
customThe solvent was removed by rotary evaporation
dissolutionthe residue dissolved in 30-40 mL CH2Cl2
additionApproximately 10 mL hexane was added
additionAdditional hexane was added dropwise until small planar white crystals
customto form
waitthe solution was refrigerated overnight
washwashed with hexane
customdried in vacuum (2.30 g, 70.0%)

Sources & evidence

ORD record: ord-26c53a69ec8e47f195c4961145fc890c
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08394813B2

Reaction notes

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