Cesium carbonate → 4-[1-(4-Trifluoromethyl-phenyl)-piperidin-4-yl]-butyric acid methyl ester

HRID 511171ノート

反応式

HRID 511171 の反応式
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.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.[CH3:54][O:55][C:56](=[O:66])[CH2:57][CH2:58][CH2:59][CH:60]1[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1.Br[C:68]1[CH:73]=[CH:72][C:71]([C:74]([F:77])([F:76])[F:75])=[CH:70][CH:69]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:54][O:55][C:56](=[O:66])[CH2:57][CH2:58][CH2:59][CH:60]1[CH2:65][CH2:64][N:63]([C:68]2[CH:73]=[CH:72][C:71]([C:74]([F:77])([F:76])[F:75])=[CH:70][CH:69]=2)[CH2:62][CH2:61]1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 634876Binap, (A+-)-HCID 66672062Methyl 4-(piperidin-4-yl)butanoate hydrochloride

生成物 1

HCID 585764494-[1-(4-Trifluoromethyl-phenyl)-piperidin-4-yl]-butyric acid methyl ester収率 64.7%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of palladium (II) acetate (42 mg; 0.185 mmol), (±)-2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (170 mg; 0.275 mmol), cesium carbonate (867 g; 2.66 mmol) in dioxane (5 mL) is placed in an ultrasonic bath for 30 minutes. 4-Piperidin-4-yl-butyric acid methyl ester hydrochloride (290 mg; 1.33 mmol, prepared in accordance with Example 131) and 1-bromo-4-trifluoromethyl-benzene (299 mg; 1.33 mmol) are then added and the reaction mixture is stirred for 2 hours under reflux. After dilution with ethyl acetate, the mixture is filtered and the filtrate concentrated under high vacuum. The obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100) to afford the desired compound (284 mg; 0.86 mmol).

後処理

  1. temperatureunder reflux
  2. filtrationAfter dilution with ethyl acetate, the mixture is filtered
  3. concentrationthe filtrate concentrated under high vacuum
  4. customThe obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100)

出典と根拠

ORDレコード
ord-a3fa80e85c514e58933896c8e38f084c
出典データセット
uspto-grants-2015_08
特許番号
US09096524B2

反応ノート

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