Dicyclohexylcarbodiimide → (R)-quinuclidin-3-yl 2-(3-fluorophenyl)-2-(phenylamino)acetate

HRID 1255056Notes

Reaction equation

HRID 1255056 reaction equation
C1CCC(N=C=NC2CCCCC2)CC1.Cl.[F:17][C:18]1[CH:19]=[C:20]([CH:24]([NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:25]([OH:27])=[O:26])[CH:21]=[CH:22][CH:23]=1.C1C=CC2N(O)N=NC=2C=1.[N:45]12[CH2:52][CH2:51][CH:48]([CH2:49][CH2:50]1)[C@@H:47](O)[CH2:46]2>C1COCC1>[N:45]12[CH2:52][CH2:51][CH:48]([CH2:49][CH2:50]1)[C@@H:47]([O:26][C:25](=[O:27])[CH:24]([C:20]1[CH:21]=[CH:22][CH:23]=[C:18]([F:17])[CH:19]=1)[NH:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:46]2

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 67124831HCID 67124831, compound

Product 1

HCID 58556978(R)-quinuclidin-3-yl 2-(3-fluorophenyl)-2-(phenylamino)acetateYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

PS-DCC (982 mg, 1.31 mmol, loading: 1.33 mmol/g) is suspended in dry THF (15 mL). (3-fluoro-phenyl)-phenylamino-acetic acid hydrochloride (I98) (184 mg, 0.65 mmol), HOBT (200 mg, 1.31 mmol), and (R)-quinuclidin-3-ol (249 mg, 1.96 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 NaHCO3, water and brine. The organic layer is dried over Na2SO4, filtered and evaporated to dryness. The crude compound is purified by filtration through a pad of silica-gel using DCM/MeOH=9/1 as the eluent. The title compound is obtained as a colorless oil (129 mg, 56% 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 NaHCO3, water and brine
  5. dry with materialThe organic layer is dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. filtrationThe crude compound is purified by filtration through a pad of silica-gel

Sources & evidence

ORD record
ord-eae2c659648d41dfbe61174fcd6fef24
Source dataset
uspto-grants-2013_06
Patent number
US08455646B2

Reaction notes

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