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

HRID 1044044Notes

Reaction equation

HRID 1044044 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>[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]([O:27][C@@H:47]2[CH:48]3[CH2:51][CH2:52][N:45]([CH2:50][CH2:49]3)[CH2:46]2)=[O:26])[CH:21]=[CH:22][CH:23]=1

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) was suspended in dry THF (15 ml). 2-(3-Fluorophenyl)-2-(phenylamino)acetic acid hydrochloride (I17) (184 mg, 0.65 mmol), HOBT (200 mg, 1.31 mmol), and (R)-quinuclidin-3-ol (249 mg, 1.96 mmol) were added, and the mixture was shaken at room temperature overnight. PS-DCC was removed by filtration, and the filtrate is evaporated. The residue was dissolved in EtOAc and washed with NaHCO3, water and brine. The organic layer was dried over Na2SO4, filtered, and evaporated to dryness. The crude compound was purified by filtration through a pad of silica-gel using DCM/MeOH=9/1 as the eluent. The title compound was obtained (129 mg, 56% yield, mixture of diastereomers).

Workup

  1. customPS-DCC was removed by filtration
  2. customthe filtrate is evaporated
  3. dissolutionThe residue was dissolved in EtOAc
  4. washwashed with NaHCO3, water and brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. filtrationThe crude compound was purified by filtration through a pad of silica-gel

Sources & evidence

ORD record
ord-143b2466e3c645319cfab185e67cf7e2
Source dataset
uspto-grants-2013_10
Patent number
US08563577B2

Reaction notes

Loading…