Dicyclohexylcarbodiimide → HCID 46840710, compound

HRID 76994Notes

Reaction equation

HRID 76994 reaction equation
C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.Cl.[CH2:27]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[NH:35][CH:36]([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C:37]([OH:39])=[O:38])[CH3:28].[N:46]12[CH2:53][CH2:52][CH:49]([CH2:50][CH2:51]1)[C@@H:48](O)[CH2:47]2>C1COCC1>[N:46]12[CH2:53][CH2:52][CH:49]([CH2:50][CH2:51]1)[C@@H:48]([O:38][C:37](=[O:39])[CH:36]([NH:35][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=1[CH2:27][CH3:28])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[CH2:47]2

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 67424496(2-Ethyl-phenylamino)-phenyl-acetic acid hydrochloride

Product 1

HCID 46840710HCID 46840710, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

PS-DCC (962 mg, 1.37 mmol, loading: 1.33 mmol/g) is suspended in THF (10 mL). HOBT (210 mg, 1.37 mmol), (2-ethyl-phenylamino)-phenyl-acetic acid hydrochloride (160) (200 mg, 0.68 mmol), and (R)-quinuclidin-3-ol (262 mg, 2.06 mmol) are added and the mixture is shaken at RT overnight. PS-DCC is filtered off and washed with THF and the filtrate is evaporated under reduced pressure. The resulting residue is dissolved in EtOAc and washed with sat. NaHCO3, water and brine. The organic layer is separated, dried over Na2SO4, filtered and evaporated. The residue is first purified by flash chromatography (DCM/MeOH=9/1) and then by preparative HPLC. The fractions containing the product are pooled, concentrated under vacuum, basified with sat. NaHCO3 and extracted with EtOAc. The organic layer is dried (Na2SO4), filtered and evaporated to afford the title compound as a colorless oil (52 mg, 21% yield, mixture of diastereoisomers).

Workup

  1. filtrationPS-DCC is filtered off
  2. washwashed with THF
  3. customthe filtrate is evaporated under reduced pressure
  4. dissolutionThe resulting residue is dissolved in EtOAc
  5. washwashed with sat. NaHCO3, water and brine
  6. customThe organic layer is separated
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue is first purified by flash chromatography (DCM/MeOH=9/1)
  11. additionThe fractions containing the product
  12. concentrationconcentrated under vacuum
  13. extractionextracted with EtOAc
  14. dry with materialThe organic layer is dried (Na2SO4)
  15. filtrationfiltered
  16. customevaporated

Sources & evidence

ORD record
ord-17f385bb58c34ee4988f82c00b527154
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Reaction notes

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