Dicyclohexylcarbodiimide → (3-ethyl-phenylamino)-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester

HRID 76986Notes

Reaction equation

HRID 76986 reaction equation
C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.Cl.[CH2:27]([C:29]1[CH:30]=[C:31]([NH:35][CH:36]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:37]([OH:39])=[O:38])[CH:32]=[CH:33][CH:34]=1)[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:31]1[CH:32]=[CH:33][CH:34]=[C:29]([CH2:27][CH3:28])[CH:30]=1)[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 67425860(3-Ethyl-phenylamino)-phenyl-acetic acid hydrochloride

Product 1

HCID 46840575(3-ethyl-phenylamino)-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)esterYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

PS-DCC (1097 mg, 1.371 mmol, loading: 1.25 mmol/g) is suspended in THF (15 mL). HOBT (210 mg, 1.37 mmol), (3-ethyl-phenylamino)-phenyl-acetic acid hydrochloride (I42) (200 mg, 0.68 mmol), and (R)-quinuclidin-3-ol (262 mg, 2.06 mmol) are added and the suspension is shaken at RT for 16 hours. PS-DCC is filtered off and the filtrate is evaporated. The resulting residue is dissolved in EtOAc and washed with water, sat. NaHCO3, water and brine. The organic phase is dried over Na2SO4, filtered and evaporated. The crude is purified by flash chromatography (DCM/MeOH=95/5) to obtain the title compound as a colorless oil (72 mg, 30% yield, mixture of diastereoisomers).

Workup

  1. filtrationPS-DCC is filtered off
  2. customthe filtrate is evaporated
  3. dissolutionThe resulting residue is dissolved in EtOAc
  4. washwashed with water, sat. NaHCO3, water and brine
  5. dry with materialThe organic phase is dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude is purified by flash chromatography (DCM/MeOH=95/5)

Sources & evidence

ORD record
ord-1f3a6cc3dc38423e9bda5130b9d8ad60
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Reaction notes

Loading…