1,2-Dichloroethane → 1,2-Diphenylethyl quinuclidine-3-carboxylate

HRID 1910482

Reaction equation

HRID 1910482 reaction equation
Cl.[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[CH:4]([C:10]([OH:12])=[O:11])[CH2:3]2.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[C:27]1([CH:33](O)[CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CN(C=O)C.O>[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[CH:4]([C:10]([O:12][CH:33]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:11])[CH2:3]2

Participants

7

Reactant 4

HCID 111,2-Dichloroethane2×HCID 757711-Hydroxybenzotriazole2×HCID 941781,2-DiphenylethanolHCID 126734361-Azabicyclo(2.2.2)octane-3-carboxylic acid hydrochloride2×

Product 1

HCID 709258251,2-Diphenylethyl quinuclidine-3-carboxylateYield 53.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Quinuclidine-3-carboxylic acid hydrochloride (160 mg, 0.83 mmol), EDC (290 mg, 1.51 mmol), and HOBT (232 mg, 1.51 mmol) were dissolved in dry DMF (8 ml). 1,2-Diphenylethanol (150 mg, 0.76 mmol) and TEA (0.32 ml, 2.27 mmol) were added, and the resulting mixture was stirred at room temperature overnight. Then quinuclidine-3-carboxylic acid hydrochloride (72.5 mg, 0.38 mmol), EDC (87 mg, 0.45 mmol), and HOBT (57.9 mg, 0.38 mmol) were added followed by TEA (0.16 ml, 1.13 mmol), and the mixture was stirred for additional 32 hours. The mixture was diluted with water and extracted three times with Et2O. The organic phases were collected, washed with brine, dried over Na2SO4, filtered, and evaporated to dryness. The crude residue was purified by flash chromatography (DCM/MeOH=9/1) to obtain 1,2-diphenylethyl quinuclidine-3-carboxylate (136 mg, racemic mixture).

Workup

  1. stirringthe mixture was stirred for additional 32 hours
  2. extractionextracted three times with Et2O
  3. customThe organic phases were collected
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe crude residue was purified by flash chromatography (DCM/MeOH=9/1)

Sources & evidence

ORD record
ord-687d831e5a4746f0b6410cf4c63f170c
Source dataset
uspto-grants-2013_12
Patent number
US08604015B2

Linked notes

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