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

HRID 77085

反応式

HRID 77085 の反応式
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]

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-b95f706ee3ab458cbcb2d7fcd3e7a7e9
出典データセット
uspto-grants-2014_09
特許番号
US08835648B2

関連ノート

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