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

HRID 1910506

반응식

HRID 1910506 반응식
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

참가 물질

9

반응물 6

HCID 111,2-Dichloroethane3회HCID 757711-Hydroxybenzotriazole2회HCID 81531Diisopropylethylamine3회HCID 1230494,4'-Difluorobenzhydryl alcoholHCID 516892Sodium BicarbonateHCID 126734361-Azabicyclo(2.2.2)octane-3-carboxylic acid hydrochloride3회

생성물 1

HCID 70925939Bis(4-fluorophenyl)methyl quinuclidine-3-carboxylate수율 31.7%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b2193eaa529447968246abbdf8cb4ad7
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08604015B2

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