Dicyclohexylcarbodiimide → (4-chloro-phenyl)-phenylamino-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester

HRID 1255089Notes

Reaction equation

HRID 1255089 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.[N:44]12[CH2:51][CH2:50][CH:47]([CH2:48][CH2:49]1)[C@@H:46](O)[CH2:45]2>C1COCC1>[N:44]12[CH2:51][CH2:50][CH:47]([CH2:48][CH2:49]1)[C@@H:46]([O:10][C:9](=[O:11])[CH:8]([C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)[NH:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[CH2:45]2

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 2757838(4-Chloro-phenyl)-phenylamino-acetic acid

Product 1

HCID 59401101(4-chloro-phenyl)-phenylamino-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)esterYield 25.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(4-Chloro-phenyl)-phenylamino-acetic acid (I256) (1.22 g, 4.97 mmol), HOBT (0.99 g, 6.46 mmol) and DCC (1.33 g, 6.46 mmol) are dissolved in THF (250 mL). The reaction is stirred for 15 minutes and then (R)-quinuclidin-3-ol (1.26 g, 9.93 mmol) is added. The reaction is stirred at RT for 4 days. The solvent is evaporated and the residue is taken up with EtOAc. The insoluble is filtered off, the solution is washed with 1M K2CO3 and brine. The organic phase is dried (Na2SO4), filtered and evaporated to dryness. The crude is purified by flash chromatography (DCM/MeOH=98/2 to 90/10) to afford compound C259 as a yellow solid (462 mg, 25% yield).

Workup

  1. stirringThe reaction is stirred at RT for 4 days
  2. customThe solvent is evaporated
  3. filtrationThe insoluble is filtered off
  4. washthe solution is washed with 1M K2CO3 and brine
  5. dry with materialThe organic phase is dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe crude is purified by flash chromatography (DCM/MeOH=98/2 to 90/10)
  9. customto afford compound

Sources & evidence

ORD record
ord-3738e033060243d2a847055c82d5aabf
Source dataset
uspto-grants-2013_06
Patent number
US08455646B2

Reaction notes

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