1,2-Dichloroethane → Bis(4-fluorophenyl)methyl quinuclidine-3-carboxylate

HRID 1910506

Reaktionsgleichung

Reaktionsgleichung von HRID 1910506
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.[F:27][C:28]1[CH:33]=[CH:32][C:31]([CH:34]([C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)O)=[CH:30][CH:29]=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:34]([C:31]1[CH:32]=[CH:33][C:28]([F:27])=[CH:29][CH:30]=1)[C:36]1[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=1)=[O:11])[CH2:3]2

Komponenten

9

Edukt 6

HCID 111,2-Dichloroethane3×HCID 757711-Hydroxybenzotriazole2×HCID 81531Diisopropylethylamine3×HCID 1230494,4'-Difluorobenzhydryl alcoholHCID 516892Sodium BicarbonateHCID 126734361-Azabicyclo(2.2.2)octane-3-carboxylic acid hydrochloride3×

Produkt 1

HCID 70925939Bis(4-fluorophenyl)methyl quinuclidine-3-carboxylateAusbeute 31,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3283Diethyl EtherLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Quinuclidine-3-carboxylic acid hydrochloride (96 mg, 0.50 mmol), EDC (131 mg, 0.68 mmol), and HOBT (104 mg, 0.68 mmol) were suspended in dry DMF (5 ml). Bis(4-fluorophenyl)methanol (100 mg, 0.45 mmol) and DIPEA (278 μl, 1.59 mmol) were added, and the mixture was stirred at room temperature for 24 hours. Then, quinuclidine-3-carboxylic acid hydrochloride (43.5 mg, 0.23 mmol), EDC (43.5 mg, 0.23 mmol), HOBT (34.8 mg, 0.23 mmol), and DIPEA (79 μl, 0.45 mmol) were added again and stirring was continued for 4 days. Finally quinuclidine-3-carboxylic acid hydrochloride (43.5 mg, 0.23 mmol), EDC (43.5 mg, 0.23 mmol), and DIPEA (79 μl, 0.45 mmol) were added, and the suspension was stirred for additional 24 hours. The reaction was portioned between sat. NaHCO3 and Et2O, and the organic layer was separated, washed again with sat. NaHCO3 and then brine. The organic phase was dried over Na2SO4, filtered, and evaporated to afford bis(4-fluorophenyl)methyl quinuclidine-3-carboxylate (51 mg, racemic mixture). The compound was used as such in the next step.

Aufarbeitung

  1. stirringstirring
  2. waitwas continued for 4 days
  3. stirringthe suspension was stirred for additional 24 hours
  4. customthe organic layer was separated
  5. washwashed again with sat. NaHCO3
  6. dry with materialThe organic phase was dried over Na2SO4
  7. filtrationfiltered
  8. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-b2193eaa529447968246abbdf8cb4ad7
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08604015B2

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