Dicyclohexylcarbodiimide → (2,5-Dimethoxy-phenylamino)-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester

HRID 76992Notes

Reaction equation

HRID 76992 reaction equation
C1CCC(N=C=NC2CCCCC2)CC1.Cl.[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=1[NH:27][CH:28]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:29]([OH:31])=[O:30].C1C=CC2N(O)N=NC=2C=1.[N:48]12[CH2:55][CH2:54][CH:51]([CH2:52][CH2:53]1)[C@@H:50](O)[CH2:49]2>C1COCC1>[N:48]12[CH2:55][CH2:54][CH:51]([CH2:52][CH2:53]1)[C@@H:50]([O:30][C:29](=[O:31])[CH:28]([NH:27][C:20]1[CH:21]=[C:22]([O:25][CH3:26])[CH:23]=[CH:24][C:19]=1[O:18][CH3:17])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:49]2

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 67425639(2,5-Dimethoxy-phenylamino)-phenyl-acetic acid hydrochloride

Product 1

HCID 46840708(2,5-Dimethoxy-phenylamino)-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)esterYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

PS-DCC (715 mg, 0.951 mmol, loading: 1.33 mmol/g) is suspended in dry THF (10 mL). (2,5-Dimethoxy-phenylamino)-phenyl-acetic acid hydrochloride (I54) (154 mg, 0.48 mmol), HOBT (146 mg, 0.95 mmol) and (R)-quinuclidin-3-ol (181 mg, 1.43 mmol) are added and the mixture is shaken at RT overnight. PS-DCC is filtered off and the filtrate is evaporated. The residue is dissolved in EtOAc and washed with sat. NaHCO3, water and brine. The organic layer is dried over Na2SO4, filtered and evaporated to dryness. The crude compound is purified by flash chromatography (DCM/MeOH=95/5) to achieve the title compound as a colorless oil (108 mg, 57% yield, mixture of diastereoisomers).

Workup

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

Sources & evidence

ORD record
ord-858f759d6ad748e999ab8b1ab188f5e7
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Reaction notes

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