Morpholine → HCID 86699753、化合物

HRID 515186ノート

反応式

HRID 515186 の反応式
Br[C:2]1[CH:9]=[C:8]([CH3:10])[C:5]([C:6]#[N:7])=[C:4]([O:11][CH3:12])[CH:3]=1.[NH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[Cs+].[Cs+].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>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH3:12][O:11][C:4]1[CH:3]=[C:2]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[CH:9]=[C:8]([CH3:10])[C:5]=1[C:6]#[N:7]

参加物

8

反応物 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 454803844-bromo-2-methoxy-6-methylbenzonitrile

生成物 1

HCID 86699753HCID 86699753、化合物収率 29%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
40 °C

実験手順

A solution of 4-bromo-2-methoxy-6-methyl-benzonitrile (synthesized according to the methods described in sections a) and b) of example 10) (2.0 g, 8.85 mmol), morpholine (1.2 ml, 12.8 mmol) and caesium carbonate (3.9 g, 12.0 mmol) in toluene (75 ml) is degassed and flushed with argon for 30 min and the mixture is heated to 40° C. followed by the addition of tris(dibenzylideneacetone)-dipalladium(0) (0.37 g, 0.39 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.55 g, 0.88 mmol). The resulting mixture is stirred at 110° C. for 16 h. After completion of the reaction (monitored by TLC), the mixture is poured into water (60 ml) and extracted with ethyl acetate (3×50 ml).The combined organic layers are washed with water (2×50 ml), brine (2×30 ml), dried over sodium sulfate and concentrated in vacuo. The crude product is purified by flash column chromatography (silica gel, 25% ethyl acetate/hexane) affording 2-methoxy-6-methyl-4-morpholin-4-yl-benzonitrile (0.6 g, 2.58 mmol, 29%).

後処理

  1. customis degassed
  2. customflushed with argon for 30 min
  3. customAfter completion of the reaction (monitored by TLC)
  4. extractionextracted with ethyl acetate (3×50 ml).The combined organic layers
  5. washare washed with water (2×50 ml), brine (2×30 ml)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe crude product is purified by flash column chromatography (silica gel, 25% ethyl acetate/hexane)

出典と根拠

ORDレコード
ord-b9f1362256f24bbab7defc92f686036e
出典データセット
uspto-grants-2015_08
特許番号
US09108936B2

反応ノート

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