Cesium carbonate → 4-Acetyl-6-chloro-3-ethoxy-2-(3-methoxyazetidin-1-yl)benzonitrile

HRID 1499924ノート

反応式

HRID 1499924 の反応式
[C:1]([C:4]1[CH:11]=[C:10]([Cl:12])[C:7]([C:8]#[N:9])=[C:6](I)[C:5]=1[O:14][CH2:15][CH3:16])(=[O:3])[CH3:2].Cl.[CH3:18][O:19][CH:20]1[CH2:23][NH:22][CH2:21]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([C:4]1[CH:11]=[C:10]([Cl:12])[C:7]([C:8]#[N:9])=[C:6]([N:22]2[CH2:23][CH:20]([O:19][CH3:18])[CH2:21]2)[C:5]=1[O:14][CH2:15][CH3:16])(=[O:3])[CH3:2]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 222428583-Methoxyazetidine hydrochlorideHCID 866669594-Acetyl-6-chloro-3-ethoxy-2-iodobenzonitrile

生成物 1

HCID 866778424-Acetyl-6-chloro-3-ethoxy-2-(3-methoxyazetidin-1-yl)benzonitrile収率 97.2%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

To a mixture of 4-acetyl-6-chloro-3-ethoxy-2-iodobenzonitrile (50 mg, 0.1 mmol, Example 318, Step 1), 3-methoxyazetidine hydrochloride (21 mg, 0.17 mmol Chem-Impex catalog#20140) and cesium carbonate (70.0 mg, 0.21 mmol) in 1,4-dioxane (4 mL) was added (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (40 mg, 0.07 mmol) and tris(dibenzylideneacetone)dipalladium (0) (60 mg, 0.07 mmol). The reaction mixture was degassed with N2. The reaction was heated at 80° C. for 2 hrs and was monitored by LC/MS. The reaction was allowed to cool to room temperature, was diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated to give the crude product. The product was purified by FCC on silica gel eluting (hexanes: EtOAc 0-70%) gradient to give to 4-acetyl-6-chloro-3-ethoxy-2-(3-methoxyazetidin-1-yl)benzonitrile as clear oil (0.030 g, 70%). LCMS calculated for C15H18ClN2O3(M+H)+: m/z=309.1; found: 309.1.

後処理

  1. customThe reaction mixture was degassed with N2
  2. temperatureto cool to room temperature
  3. additionwas diluted with water
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude product
  10. customThe product was purified by FCC on silica gel eluting (hexanes: EtOAc 0-70%) gradient

出典と根拠

ORDレコード
ord-69f7b619addd4ba98c30fb179fb81683
出典データセット
uspto-grants-2015_12
特許番号
US09199982B2

反応ノート

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