4-Piperidinecarboxylic acid → 1-[3-(1-Methyl-1H-benzoimidazol-2-yl)-phenyl]-piperidine-4-carboxylic acid ethyl ester

HRID 77085

반응식

HRID 77085 반응식
Br[C:2]1[CH:3]=[C:4]([C:8]2[N:12]([CH3:13])[C:11]3[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[NH:18]1[CH2:23][CH2:22][CH:21]([C:24]([OH:26])=[O:25])[CH2:20][CH2:19]1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH:33]1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=C[CH:38]=1>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH2:33]([O:25][C:24]([CH:21]1[CH2:22][CH2:23][N:18]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([C:8]3[N:12]([CH3:13])[C:11]4[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=4[N:9]=3)[CH:3]=2)[CH2:19][CH2:20]1)=[O:26])[CH3:38]

참가 물질

8

반응물 4

HCID 37734-Piperidinecarboxylic acidHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 9624512-(3-bromophenyl)-1-methyl-1H-benzimidazole

생성물 1

HCID 669775251-[3-(1-Methyl-1H-benzoimidazol-2-yl)-phenyl]-piperidine-4-carboxylic acid ethyl ester수율 55%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

Method 11—Step a 2-(3-Bromo-phenyl)-1-methyl-1H-benzoimidazole (obtained as described in general method 1, step b) (5.00 g, 17.40 mmol), piperidine-4-carboxylic acid esthyl ester (3.56 g, 22.62 mmol) and cesium carbonate (28.34 g, 87 mmol) were placed into a round bottom flask under nitrogen. At the same time palladium acetate (0.79 g, 3.48 mmol), and BINAP (3.33 g, 5.22 mmol) were placed into a flask under nitrogen. Then dry toluene (18 mL) was added and the mixture was stirred 20 minutes under nitrogen before being added to the first flask. The reaction mixture was heated at 80° C. for two days, then diluted with ethyl acetate (100 mL), filtered through Na2SO4, and washed with water (2×50 mL) and brine (1×50 mL). The organic solution was concentrated under reduced pressure and crude was purified by flash chromatography (eluent: cyclohexane:AcOEt/4:1) to afford 3.45 g of the title compound (55%).

후처리

  1. additionbefore being added to the first flask
  2. filtrationfiltered through Na2SO4
  3. washwashed with water (2×50 mL) and brine (1×50 mL)
  4. concentrationThe organic solution was concentrated under reduced pressure and crude
  5. customwas purified by flash chromatography (eluent: cyclohexane:AcOEt/4:1)

출처 및 근거

ORD 기록
ord-b95f706ee3ab458cbcb2d7fcd3e7a7e9
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835648B2

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