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

HRID 1910507Notes

Reaction equation

HRID 1910507 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]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)O)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOCC>[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)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:11])[CH2:3]2

Participants

9

Reactant 6

HCID 111,2-Dichloroethane2×HCID 7037BenzhydrolHCID 757711-Hydroxybenzotriazole2×HCID 81531Diisopropylethylamine2×HCID 516892Sodium BicarbonateHCID 126734361-Azabicyclo(2.2.2)octane-3-carboxylic acid hydrochloride2×

Product 1

HCID 70926085Benzhydryl quinuclidine-3-carboxylateYield 31.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

Quinuclidine-3-carboxylic acid hydrochloride (114 mg, 0.60 mmol), EDC (156 mg, 0.81 mmol), and HOBT (125 mg, 0.81 mmol) were suspended in dry DMF (5 ml). Diphenylmethanol (100 mg, 0.54 mmol) and DIPEA (332 μl, 1.90 mmol) were added, and the mixture was stirred at room temperature for 24 hours. Quinuclidine-3-carboxylic acid hydrochloride (52.0 mg, 0.27 mmol), EDC (52.0 mg, 0.27 mmol), and HOBT (41.6 mg, 0.27 mmol) followed by DIPEA (95 μl, 0.54 mmol) were added again, and the mixture was stirred for 4 days. The reaction was then portioned between sat. NaHCO3 and Et2O. The organic layer was separated, washed again with sat. NaHCO3, water and brine, dried over Na2SO4, filtered, and evaporated to afford benzhydryl quinuclidine-3-carboxylate (54 mg, racemic mixture). The compound was used as such in the next step.

Workup

  1. additionwere added again
  2. stirringthe mixture was stirred for 4 days
  3. customThe organic layer was separated
  4. washwashed again with sat. NaHCO3, water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-eff67eb648aa4ff1bc159a4e95e699b4
Source dataset
uspto-grants-2013_12
Patent number
US08604015B2

Reaction notes

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