Cesium carbonate → HCID 66977738, compound

HRID 77081Notes

Reaction equation

HRID 77081 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][C:15]([CH3:17])=[CH:16][C:11]=2[N:10]=[C:9]1[C:18]1[CH:23]=[C:22](Br)[CH:21]=[CH:20][C:19]=1[F:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:26]([O:28][C:29]([CH:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1)=[O:30])[CH3:27].C(=O)([O-])[O-].[Cs+].[Cs+].C1C=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)=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][C:15]([CH3:17])=[CH:16][C:11]=2[N:10]=[C:9]1[C:18]1[CH:23]=[C:22]([N:34]2[CH2:35][CH2:36][CH:31]([C:29]([O:28][CH2:26][CH3:27])=[O:30])[CH2:32][CH2:33]2)[CH:21]=[CH:20][C:19]=1[F:25])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 70770Ethyl 4-piperidinecarboxylateHCID 634876Binap, (A+-)-HCID 66977753HCID 66977753, compound

Product 1

HCID 66977738HCID 66977738, compoundYield 99.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
80 °C

Procedure

Method 8—Step a 2-(5-Bromo-2-fluoro-phenyl)-5-methyl-benzoimidazole-1-carboxylic acid tert-butyl ester (obtained as described in general method 6, step c) (0.94 g, 2.40 mmol), piperidine-4-carboxylic acid ethyl ester (0.48 g, 3.12 mmol) and cesium carbonate (3.90 g, 12.01 mmol) were placed into a dried schlenk tube and 3 cycles of vacuum/nitrogen were performed, then dry toluene (4 mL) was added. At the same time palladium(II)acetate (0.82 g, 0.36 mmol), and BINAP (0.45 g, 0.72 mmol) were placed into a dried schlenk tube under nitrogen and 3 cycles of vacuum/nitrogen were performed. Then dry toluene (2 mL) was added, at room temperature under nitrogen, and the mixture was added to the first schlenk. The reaction mixture was heated at 80° C. overnight, water (5 mL) was added, the organic layer was filtered over Na2SO4 and then purified by flash chromatography (eluent: cyclohexane:EtOAc 8:2) to obtain 1.15 g of the title compound in quantitative yield.

Workup

  1. additionthe mixture was added to the first schlenk
  2. filtrationthe organic layer was filtered over Na2SO4
  3. custompurified by flash chromatography (eluent: cyclohexane:EtOAc 8:2)

Sources & evidence

ORD record
ord-d1ac83c2948a4371b4c52bc30731a7b1
Source dataset
uspto-grants-2014_09
Patent number
US08835648B2

Reaction notes

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