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

HRID 1044056Notes

Reaction equation

HRID 1044056 reaction equation
[CH3:1][N:2]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4]([OH:6])=[O:5].[N:19]12[CH2:26][CH2:25][CH:22]([CH2:23][CH2:24]1)[C@@H:21](O)[CH2:20]2.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1>[CH3:1][N:2]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4]([O:6][C@@H:21]1[CH:22]2[CH2:25][CH2:26][N:19]([CH2:24][CH2:23]2)[CH2:20]1)=[O:5]

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 20993142HCID 20993142, compound

Product 1

HCID 46840263(R)-quinuclidin-3-yl 2-(methyl(phenyl)amino)-2-phenylacetateYield 68.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(Methyl(phenyl)amino)-2-phenylacetic acid (I35) (2.20 g, 9.12 mmol) was dissolved in THF (25 ml), and (R)-quinuclidin-3-ol (1.28 g, 10.0 mmol) was added. To the resulting solution, HOBt (1.23 g, 9.12 mmol) and DCC (1.88 g, 9.12 mmol) were added, and the mixture was stirred at room temperature for three days. THF was removed under vacuum and the residue was portioned between H2O and EtOAc. The organic phase was washed with a saturated aqueous Na2CO3 solution, dried over Na2SO4 and evaporated to dryness. The crude was purified by flash chromatography (EtOAc to EtOAc/MeOH=75/25) to afford (R)-quinuclidin-3-yl 2-(methyl(phenyl)amino)-2-phenylacetate (2.2 g, 68.8% yield, mixture of diastereomers).

Workup

  1. customTHF was removed under vacuum
  2. washThe organic phase was washed with a saturated aqueous Na2CO3 solution
  3. dry with materialdried over Na2SO4
  4. customevaporated to dryness
  5. customThe crude was purified by flash chromatography (EtOAc to EtOAc/MeOH=75/25)

Sources & evidence

ORD record
ord-9edc687e1eef40afb6d47e5bbab87efb
Source dataset
uspto-grants-2013_10
Patent number
US08563577B2

Reaction notes

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