Cesium carbonate → Tert-butyl({1-[4-(trifluoromethyl)phenyl]piperidin-4-yl}methyl)carbamate

HRID 1047387ノート

反応式

HRID 1047387 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.[C:12]([O:16][C:17](=[O:26])[NH:18][CH2:19][CH:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)([CH3:15])([CH3:14])[CH3:13].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>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:12]([O:16][C:17](=[O:26])[NH:18][CH2:19][CH:20]1[CH2:21][CH2:22][N:23]([C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=2)[CH2:24][CH2:25]1)([CH3:15])([CH3:13])[CH3:14]

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 634876Binap, (A+-)-HCID 723429Tert-butyl (piperidin-4-ylmethyl)carbamate

生成物 1

HCID 66853254Tert-butyl({1-[4-(trifluoromethyl)phenyl]piperidin-4-yl}methyl)carbamate収率 61.8%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒2 回

反応条件

温度
110 °C

実験手順

A solution of 1-bromo-4-trifluoromethyl-benzene (50.0 g; 220 mmol) and piperidin-4-ylmethyl-carbamic acid tert-butyl ester (48.1 g; 220 mmol) in dioxane (1 L) was added to a suspension of palladium (II) acetate (7.41 g; 33 mmol), cesium carbonate (144.8 g; 440 mmol), and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (31.8 g; 45 mmol) in dioxane (1 L). The resulting mixture was heated to 110° C., and then maintained at that temperature for 28 hr with stirring. The mixture was then allowed to cool to room temperature. Afterward, the reaction mixture was treated with water (2 L) and extracted with dichloromethane (2×1 L). The combined organic phases were dried over sodium sulfate and filtered, and then the solvents were removed under reduced pressure. The resulting residue was dissolved in acetonitrile (1.5 L). Water (1.5 L) was then added with stirring. This resulting in a precipitate, which was filtered and then dried overnight at 40° C. at a pressure of 3 mbar to afford the desired product (48.9 g; 136 mmol).

後処理

  1. temperaturemaintained at that temperature for 28 hr
  2. temperatureto cool to room temperature
  3. extractionextracted with dichloromethane (2×1 L)
  4. dry with materialThe combined organic phases were dried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvents were removed under reduced pressure
  7. dissolutionThe resulting residue was dissolved in acetonitrile (1.5 L)
  8. additionWater (1.5 L) was then added
  9. stirringwith stirring
  10. filtrationThis resulting in a precipitate, which was filtered
  11. customdried overnight at 40° C. at a pressure of 3 mbar

出典と根拠

ORDレコード
ord-5b410fe0dc6541578101b8c64bdb4448
出典データセット
uspto-grants-2013_10
特許番号
US08569495B2

反応ノート

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