1,2-Dichloroethane → Bis(3-fluorophenyl)methyl quinuclidine-3-carboxylate

HRID 1910481

Reaction equation

HRID 1910481 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.CCN(C(C)C)C(C)C.[F:36][C:37]1[CH:38]=[C:39]([CH:43]([C:45]2[CH:50]=[CH:49][CH:48]=[C:47]([F:51])[CH:46]=2)O)[CH:40]=[CH:41][CH:42]=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:43]([C:39]1[CH:40]=[CH:41][CH:42]=[C:37]([F:36])[CH:38]=1)[C:45]1[CH:50]=[CH:49][CH:48]=[C:47]([F:51])[CH:46]=1)=[O:11])[CH2:3]2

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2758250Bis(3-fluorophenyl)methanolHCID 126734361-Azabicyclo(2.2.2)octane-3-carboxylic acid hydrochloride

Product 1

HCID 70925896Bis(3-fluorophenyl)methyl quinuclidine-3-carboxylateYield 57.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Quinuclidine-3-carboxylic acid hydrochloride (817 mg, 4.26 mmol), EDC (1.23 g, 6.39 mmol), and HOBT (979 mg, 6.39 mmol) were dissolved in dry DMF (40 ml). DIPEA (2.61 ml, 14.9 mmol) and bis(3-fluorophenyl)methanol (1.03 mg, 4.69 mmol) were added, and the mixture was stirred at room temperature overnight. The mixture was diluted with water and extracted several times with Et2O. The organic phases were collected and washed with brine, dried (Na2SO4), filtered, and evaporated. The residue was purified by flash chromatography (DCM/MeOH=9/1) to obtain bis(3-fluorophenyl)methyl quinuclidine-3-carboxylate (874 mg, racemic mixture).

Workup

  1. extractionextracted several times with Et2O
  2. customThe organic phases were collected
  3. washwashed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash chromatography (DCM/MeOH=9/1)

Sources & evidence

ORD record
ord-e5b17f1598fd4752a8591a206b36f7cb
Source dataset
uspto-grants-2013_12
Patent number
US08604015B2

Linked notes

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