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

HRID 423425ノート

反応式

HRID 423425 の反応式
[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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
70 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-caaafbcdee4c4c3ab3d718c11f535d20
出典データセット
uspto-grants-2012_01
特許番号
US08101764B2

反応ノート

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