Morpholine → HCID 86699740、化合物

HRID 515171ノート

反応式

HRID 515171 の反応式
Br[C:2]1[CH:18]=[C:17]([CH3:19])[C:5]([C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[O:7])=[C:4]([O:20][CH3:21])[CH:3]=1.[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.CC(C)([O-])C.[Na+].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>CN1CCCC1=O.O.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]>[F:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][NH:8][C:6](=[O:7])[C:5]2[C:17]([CH3:19])=[CH:18][C:2]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:3][C:4]=2[O:20][CH3:21])=[CH:11][CH:12]=1

参加物

8

反応物 4

HCID 8083MorpholineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 86699739HCID 86699739、化合物

生成物 1

HCID 86699740HCID 86699740、化合物収率 91%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
40 °C

実験手順

To a stirred solution of 4-bromo-N-[(4-fluorophenyl)-methyl]-2-methoxy-6-methyl-benzamide (2.7 g, 7.67 mmol) in N-methyl-2-pyrrolidone (10 ml) is added morpholine (0.93 g, 10.7 mmol) at RT. The reaction mixture is degassed and flushed with argon for 30 min followed by addition of sodium tert-butoxide (0.95 g, 9.9 mmol). The reaction mixture is heated to 40° C. At this temperature are added tris(dibenzylideneacetone)dipalladium(0) (0.31 g, 0.34 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.47 g, 0.76 mmol) and stirred at 100° C. for 12 h. After completion of the reaction (monitored by TLC), the mixture is diluted with water (50 ml) and extracted with ethyl acetate (3×75 ml). The organic layer is washed with water (50 ml), brine (50 ml), dried over anhydrous sodium sulfate and evaporated to get the crude product, which is purified by column chromatography (silica gel, 40% acetone/hexane) to yield N-[(4-fluorophenyl)-methyl]-2-methoxy-6-methyl-4-morpholin-4-yl-benzamide (2.50 g, 6.90 mmol, 91%).

後処理

  1. customThe reaction mixture is degassed
  2. customflushed with argon for 30 min
  3. customAfter completion of the reaction (monitored by TLC)
  4. extractionextracted with ethyl acetate (3×75 ml)
  5. washThe organic layer is washed with water (50 ml), brine (50 ml)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated
  8. customto get the crude product, which
  9. customis purified by column chromatography (silica gel, 40% acetone/hexane)

出典と根拠

ORDレコード
ord-02e77df3d0654ef687ece2e465bc5c79
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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