Dicyclohexylcarbodiimide → (R)-quinuclidin-3-yl 2-(methyl(phenyl)amino)-2-phenylacetate

HRID 1255038Notes

Reaction equation

HRID 1255038 reaction equation
Cl.[CH3:2][N:3]([C@H:10]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:11]([OH:13])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=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>O1CCOCC1>[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]([N:3]([CH3:2])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=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 67424971(R)-(methyl-phenyl-amino)-phenyl-acetic acid hydrochloride

Product 1

HCID 46840263(R)-quinuclidin-3-yl 2-(methyl(phenyl)amino)-2-phenylacetateYield 38%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

(R)-(Methyl-phenyl-amino)-phenyl-acetic acid hydrochloride (I74) (97 mg, 0.35 mmol), HOBT (107 mg, 0.70 mmol), DCC (144 mg, 0.70 mmol) and (R)-quinuclidin-3-ol (89 mg, 0.70 mmol) are dissolved in dioxane (5 mL) and the mixture is stirred at RT for 15 hours. The white precipitate is filtered and discarded whereas the clear solution is evaporated to dryness. The residue is dissolved in EtOAc and washed with sat. Na2CO3 and then brine. The organic phase is dried over sodium sulphate, filtered and evaporated to dryness. The resulting crude is purified by flash chromatography on silica gel (DCM/MeOH=97/3 to 95/5) to obtain the title compound as a pale yellow oil (46 mg, 38% yield, mixture of diastereoisomers).

Workup

  1. filtrationThe white precipitate is filtered
  2. customis evaporated to dryness
  3. dissolutionThe residue is dissolved in EtOAc
  4. washwashed with sat. Na2CO3
  5. dry with materialThe organic phase is dried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe resulting crude is purified by flash chromatography on silica gel (DCM/MeOH=97/3 to 95/5)

Sources & evidence

ORD record
ord-e83e71c88c6b4e1d8a994013ec52e7fa
Source dataset
uspto-grants-2013_06
Patent number
US08455646B2

Reaction notes

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