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

HRID 511171노트

반응식

HRID 511171 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-a3fa80e85c514e58933896c8e38f084c
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096524B2

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