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

HRID 76999Notes

Reaction equation

HRID 76999 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:9][CH:10]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:11]([OH:13])=[O:12])[CH:6]=[CH:7][CH:8]=1.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.[N:45]12[CH2:52][CH2:51][CH:48]([CH2:49][CH2:50]1)[C@@H:47](O)[CH2:46]2>C1COCC1>[N:45]12[CH2:52][CH2:51][CH:48]([CH2:49][CH2:50]1)[C@@H:47]([O:12][C:11](=[O:13])[CH:10]([NH:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:46]2

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 2759625(3-Methoxy-phenylamino)-phenyl-acetic acid

Product 1

HCID 46840839(3-methoxy-phenylamino)-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)esterYield 52.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(3-Methoxy-phenylamino)-phenyl-acetic acid (0.58 g, 2.25 mmol), HOBT (0.45 g, 2.93 mmol) and DCC (0.60 g, 2.93 mmol) are dissolved in THF (100 mL) and stirred at RT for 20 minutes. Then, (R)-quinuclidin-3-ol (0.57 g, 4.51 mmol) is added and the resulting reaction is stirred at the same temperature for one day. The solvent is evaporated, the residue is taken up with EtOAc and the insoluble is filtered off. The organic solution is washed with 1M K2CO3 and then with brine. The crude is purified by flash chromatography (DCM/MeOH=99/1 to 80:20) to obtain the title compound as a yellow solid (0.43 g, 52% yield, mixture of diastereoisomers).

Workup

  1. customthe resulting reaction
  2. stirringis stirred at the same temperature for one day
  3. customThe solvent is evaporated
  4. filtrationthe insoluble is filtered off
  5. washThe organic solution is washed with 1M K2CO3
  6. customThe crude is purified by flash chromatography (DCM/MeOH=99/1 to 80:20)

Sources & evidence

ORD record
ord-e106723f41654fdfb6eebf7456855841
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Reaction notes

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