Cesium carbonate → (3R,3'R)-1'-(5-Bromo-pyridin-2-yl)-3-fluoro-[1,3']bipyrrolidinyl

HRID 423425노트

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HRID 423425 반응식
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:12][CH2:11][C@H:10](OS(C)(=O)=O)[CH2:9]2)=[N:6][CH:7]=1.Cl.[F:19][C@@H:20]1[CH2:24][CH2:23][NH:22][CH2:21]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.ClCCl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:12][CH2:11][C@@H:10]([N:22]3[CH2:23][CH2:24][C@@H:20]([F:19])[CH2:21]3)[CH2:9]2)=[N:6][CH:7]=1

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 2759162(3R)-3-fluoropyrrolidine hydrochlorideHCID 86638154methanesulfonic acid (S)-1-(5-bromo-pyridin-2-yl)-pyrrolidin-3-yl ester

생성물 1

HCID 66673622(3R,3'R)-1'-(5-Bromo-pyridin-2-yl)-3-fluoro-[1,3']bipyrrolidinyl수율 39%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
70 °C

실험 절차

Dissolve methanesulfonic acid (S)-1-(5-bromo-pyridin-2-yl)-pyrrolidin-3-yl ester (3 g, 9.34 mmol) and (R)-3-fluoro-pyrrolidine hydrochloride (1.00 g, 11.21 mmol) in DMF (50 mL) and add Cs2CO3 (9.13 g, 28.02 mmol). Warm to 70° C. overnight. Dilute with dichloromethane (3×40 mL), wash with H2O (50 mL) and brine. Dry with Na2SO4, filter, and concentrate the organic solution. Purify the crude material by chromatography, eluting with 0-50% EtOAc/hexane, to give 1.14 g (39%) of (3R,3′R)-1′-(5-Bromo-pyridin-2-yl)-3-fluoro-[1,3′]bipyrrolidinyl.

후처리

  1. washwash with H2O (50 mL) and brine
  2. dry with materialDry with Na2SO4
  3. filtrationfilter
  4. concentrationconcentrate the organic solution
  5. customPurify the crude material by chromatography
  6. washeluting with 0-50% EtOAc/hexane

출처 및 근거

ORD 기록
ord-caaafbcdee4c4c3ab3d718c11f535d20
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101764B2

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