Cesium carbonate → 2-[(3R)-3-fluoro-pyrrolidin-1-yl]-6-methyl-4-morpholin-4-yl-benzonitrile

HRID 515188ノート

反応式

HRID 515188 の反応式
[C:1]([C:3]1[C:8]([CH3:9])=[CH:7][C:6]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:5][C:4]=1OS(C(F)(F)F)(=O)=O)#[N:2].[F:24][C@@H:25]1[CH2:29][CH2:28][NH:27][CH2:26]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:24][C@@H:25]1[CH2:29][CH2:28][N:27]([C:4]2[CH:5]=[C:6]([N:10]3[CH2:11][CH2:12][O:13][CH2:14][CH2:15]3)[CH:7]=[C:8]([CH3:9])[C:3]=2[C:1]#[N:2])[CH2:26]1

参加物

7

反応物 3

HCID 10796Cesium carbonateHCID 27591633-FluoropyrrolidineHCID 86699756Trifluoro-methanesulfonic acid (2-cyano-3-methyl-5-morpholin-4-yl-phenyl)ester

生成物 1

HCID 866997552-[(3R)-3-fluoro-pyrrolidin-1-yl]-6-methyl-4-morpholin-4-yl-benzonitrile収率 50.8%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 634876Binap, (A+-)-触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
90 °C

実験手順

A solution of affording trifluoro-methanesulfonic acid (2-cyano-3-methyl-5-morpholin-4-yl-phenyl)ester (0.43 g, 1.22 mmol), (3R)-3-fluoro-pyrrolidin (0.19 g, 1.47 mmol) and caesium carbonate (1.6 g, 4.92 mmol) in tetrahydrofuran (25 ml) is degassed and flushed with Argon for 30 min followed by the addition of palladium(II) acetate (6.0 mg, 0.03 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (23 mg, 0.04 mmol). The resulting mixture is stirred at 90° C. for 16 h. After completion of the reaction (monitored by TLC), the mixture is poured onto water (30 ml) and extracted with ethyl acetate (3×50 ml).The combined organic layers are washed with water (2×20 ml), brine (2×20 ml), dried over sodium sulfate and concentrated in vacuo. The crude product is purified by flash column chromatography (silica gel, 15% ethyl acetate/hexane) affording 2-[(3R)-3-fluoro-pyrrolidin-1-yl]-6-methyl-4-morpholin-4-yl-benzonitrile (0.18 g, 0.62 mmol, 50%).

後処理

  1. customflushed with Argon for 30 min
  2. customAfter completion of the reaction (monitored by TLC)
  3. additionthe mixture is poured onto water (30 ml)
  4. extractionextracted with ethyl acetate (3×50 ml).The combined organic layers
  5. washare washed with water (2×20 ml), brine (2×20 ml)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe crude product is purified by flash column chromatography (silica gel, 15% ethyl acetate/hexane)

出典と根拠

ORDレコード
ord-d2af3348a5234bbf9c3d523c757a7708
出典データセット
uspto-grants-2015_08
特許番号
US09108936B2

反応ノート

読み込み中…