Cesium carbonate → HCID 66977573, compound

HRID 77082Notes

Reaction equation

HRID 77082 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][C:15]([O:17][CH3:18])=[CH:16][C:11]=2[N:10]=[C:9]1[C:19]1[CH:24]=[C:23](Br)[CH:22]=[CH:21][C:20]=1[F:26])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:27]([O:29][C:30]([CH:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1)=[O:31])[CH3:28].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.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][C:15]([O:17][CH3:18])=[CH:16][C:11]=2[N:10]=[C:9]1[C:19]1[CH:24]=[C:23]([N:35]2[CH2:36][CH2:37][CH:32]([C:30]([O:29][CH2:27][CH3:28])=[O:31])[CH2:33][CH2:34]2)[CH:22]=[CH:21][C:20]=1[F:26])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 70770Ethyl 4-piperidinecarboxylateHCID 634876Binap, (A+-)-HCID 66977585HCID 66977585, compound

Product 1

HCID 66977573HCID 66977573, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
80 °C

Procedure

Method 9—Step a 2-(5-Bromo-2-fluoro-phenyl)-5-methoxy-benzoimidazole-1-carboxylic acid tert-butyl ester (obtained as described in general method 6, step c) (1.05 g, 2.50 mmol), piperidine-4-carboxylic acid ethyl ester (0.51 g, 3.25 mmol) and cesium carbonate (4.07 g, 12.50 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 (0.11 g, 0.50 mmol), and BINAP (0.48 g, 0.75 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, cooled to room temperature, EtOAC (20 mL) was added and the mixture filtered off. Solvent was removed and the crude was purified by flash chromatography (eluent gradient: cyclohexane:EtOAc from 4:1 to 3:1), to obtain 0.82 g of the title compound (69%).

Workup

  1. additionthe mixture was added to the first schlenk
  2. temperaturecooled to room temperature
  3. additionEtOAC (20 mL) was added
  4. filtrationthe mixture filtered off
  5. customSolvent was removed
  6. customthe crude was purified by flash chromatography (eluent gradient: cyclohexane:EtOAc from 4:1 to 3:1)

Sources & evidence

ORD record
ord-8f41893658b7438c8da5dae11a765f3b
Source dataset
uspto-grants-2014_09
Patent number
US08835648B2

Reaction notes

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