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Dicyclohexylcarbodiimide → HCID 21275452, compound

HRID 1381945
Notes
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Reaction equation

HRID 1381945 reaction equation
[ClH:1].[CH3:2][O:3][N:4]1[C:8](=[O:9])[CH2:7][C:6]2([CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[C:5]1=[O:15].C(OC([NH:23][CH2:24][CH2:25][CH2:26][C:27](O)=[O:28])=O)(C)(C)C.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O.C(N(CC)CC)C>[ClH:1].[NH2:23][CH2:24][CH2:25][CH2:26][C:27]([N:12]1[CH2:13][CH2:14][C:6]2([C:5](=[O:15])[N:4]([O:3][CH3:2])[C:8](=[O:9])[CH2:7]2)[CH2:10][CH2:11]1)=[O:28]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 2948944-(((Tert-butoxy)carbonyl)amino)butanoic acidHCID 30882852,8-Diazaspiro(4,5)decane-1,3-dione, 2-methoxy-, monohydrochloride

Product 1

HCID 21275452HCID 21275452, compoundYield 58.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent
HCID 8471TriethylamineSolvent

Procedure

To a solution of 2-methoxy-2,8-diazaspiro[4,5]decane-1,3-dione hydrochloride (1.5 g) in dimethylformamide (100 ml) were added triethylamine (1 ml), 4-(tert-butyloxycarbonylamino)butyric acid (2.03 g), N-hydroxybenztriazole (1.35 g) and dicylohexylcarbodiimide (2.06 g) in sequential additions, and this was followed by stirring at room temperature for 5 hours. The resulting precipitates were then removed. The solvent was evaporated under reduced pressure, and the resulting residual oily substance was dissolved in dichloromethane (50 ml), after which it was washed with a 10% aqueous solution of citric acid and then with water. The organic layer was then dried with anhydrous magnesium sulfate, and this was followed by the evaporation of the solvent under reduced pressure. The resulting residual oil was separated by silica gel column chromatography (eluent; chloroform-acetone-methanol=10:3:2 (v/v)). To the resulting oily substance containing the desired product was added a solution of 6N hydrogen chloride in ethanol (20 ml), and it was kept standing at room temperature for 10 minutes. The solvent was then evaporated under reduced pressure. The resulting oily substance was separated by silica gel column chromatography (eluent; chloroform-methanol-water=14:6:1) to obtain 1.2 g of a noncrystalline solid.

Workup

  1. customThe resulting precipitates
  2. customwere then removed
  3. customThe solvent was evaporated under reduced pressure
  4. dissolutionthe resulting residual oily substance was dissolved in dichloromethane (50 ml)
  5. washafter which it was washed with a 10% aqueous solution of citric acid
  6. dry with materialThe organic layer was then dried with anhydrous magnesium sulfate
  7. customthis was followed by the evaporation of the solvent under reduced pressure
  8. customThe resulting residual oil was separated by silica gel column chromatography (eluent; chloroform-acetone-methanol=10:3:2 (v/v))
  9. additionTo the resulting oily substance containing the desired product
  10. additionwas added a solution of 6N hydrogen chloride in ethanol (20 ml), and it
  11. waitwas kept standing at room temperature for 10 minutes
  12. customThe solvent was then evaporated under reduced pressure
  13. customThe resulting oily substance was separated by silica gel column chromatography (eluent; chloroform-methanol-water=14:6:1)

Sources & evidence

ORD record
ord-7c502c11627245cbb589e1b189968547
Source dataset
uspto-grants-1989_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US04804665

Reaction notes

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