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

HRID 77085

Reaction equation

HRID 77085 reaction equation
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]

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-b95f706ee3ab458cbcb2d7fcd3e7a7e9
Source dataset
uspto-grants-2014_09
Patent number
US08835648B2

Linked notes

Loading…