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

HRID 77048Notes

Reaction equation

HRID 77048 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([NH2:18])([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.[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])[C:8]([C:5]1[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=1)([NH2:18])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[CH2:45]2

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 2378904-Methyl-phenyl-amino-phenyl-acetic acid

Product 1

HCID 866432354-methyl-phenyl-amino-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-methyl-phenyl-amino-phenyl-acetic acid (I244) (870 mg, 3.60 mmol) in dry THF (35 mL), are added DCC (891 mg, 4.32 mmol), HOBt (583 mg, 4.32 mmol) and 3(R)-quinuclidinol (915 mg, 7.20 mmol). The resulting mixture is stirred at RT for 48 hours (UPLC-MS monitoring: complete conversion). The solvent is evaporated and the residue is portioned between EtOAc and 1M K2CO3. The organic phase is dried over Na2SO4, filtered and evaporated to dryness. The resulting crude is dissolved in little DCM and filtered to remove the insoluble. The solution is concentrated under vacuum to obtain the title compound as a yellow solid, which is used in the next step without any further purification.

Workup

  1. customThe solvent is evaporated
  2. dry with materialThe organic phase is dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated to dryness
  5. dissolutionThe resulting crude is dissolved in little DCM
  6. filtrationfiltered
  7. customto remove the insoluble
  8. concentrationThe solution is concentrated under vacuum

Sources & evidence

ORD record
ord-8cfcf523a0414df081648c10a7ce2e3d
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Reaction notes

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