Potassium Phosphate, Tribasic → HCID 117660497, compound

HRID 1428396Notes

Reaction equation

HRID 1428396 reaction equation
Br[C:2]1[CH:23]=[CH:22][C:5]2[N:6]([CH2:19][O:20][CH3:21])[C:7]([CH2:9][N:10]([CH3:18])[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[N:8][C:4]=2[CH:3]=1.BrC1C=CC2N=C(CN(C)C(=O)O[C:37]([CH3:40])(C)[CH3:38])N(COC)C=2C=1.C1(B(O)O)CC1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1.O>[CH:40]1([C:2]2[CH:23]=[CH:22][C:5]3[N:6]([CH2:19][O:20][CH3:21])[C:7]([CH2:9][N:10]([CH3:18])[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[N:8][C:4]=3[CH:3]=2)[CH2:37][CH2:38]1

Participants

9

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 117660496HCID 117660496, compoundHCID 117660498HCID 117660498, compound

Product 1

HCID 117660497HCID 117660497, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 22272177Toluene waterSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of a mixture (1.25 g) of tert-butyl {[5-bromo-1-(methoxymethyl)-1H-benzimidazol-2-yl]methyl}methylcarbamate and tert-butyl {[6-bromo-1-(methoxymethyl)-1H-benzimidazol-2-yl]methyl}methylcarbamate and toluene/water (20/1, 26.3 mL) were added cyclopropylboronic acid (840 mg), palladium (II) acetate (146 mg), tricyclohexylphosphine (365 mg), and potassium phosphate (4.14 g), followed by heating and stirring at 100° C. overnight. The reaction mixture was diluted with EtOAc, and washed with water, 1 M hydrochloric acid solution, and brine in this order. The organic layer was dried over Na2SO4 and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: Hex/EtOAc=80/20-55/45) to obtain a mixture (505 mg) of tert-butyl {[5-cyclopropyl-1-(methoxymethyl)-1H-benzimidazol-2-yl]methyl}methylcarbamate and tert-butyl {[6-cyclopropyl-1-(methoxymethyl)-1H-benzimidazol-2-yl]methyl}methylcarbamate.

Workup

  1. temperatureby heating
  2. washwashed with water, 1 M hydrochloric acid solution, and brine in this order
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (eluent: Hex/EtOAc=80/20-55/45)

Sources & evidence

ORD record
ord-ed406748119043d6bb02a4d6742fef6a
Source dataset
uspto-grants-2015_01
Patent number
US08937087B2

Reaction notes

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