1,8-Diazabicyclo(5.4.0)undec-7-ene → Ethyl 2-({[1-(biphenyl-4-ylmethyl)-4,6-difluoro-5-iodo-1H-benzimidazol-2-yl]oxy}methyl)cyclopropanecarboxylate

HRID 340798

Reaction equation

HRID 340798 reaction equation
[C:1]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:6]=[CH:5][C:4]([CH2:7][N:8]2[C:12]3[CH:13]=[C:14]([F:19])[C:15]([I:18])=[C:16]([F:17])[C:11]=3[N:10]=[C:9]2S(C)(=O)=O)=[CH:3][CH:2]=1.[CH2:30]([O:32][C:33]([CH:35]1[CH2:37][CH:36]1[CH2:38][OH:39])=[O:34])[CH3:31].C1CCN2C(=NCCC2)CC1>CN(C=O)C.CCOC(C)=O.O>[C:1]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:6]=[CH:5][C:4]([CH2:7][N:8]2[C:12]3[CH:13]=[C:14]([F:19])[C:15]([I:18])=[C:16]([F:17])[C:11]=3[N:10]=[C:9]2[O:39][CH2:38][CH:36]2[CH2:37][CH:35]2[C:33]([O:32][CH2:30][CH3:31])=[O:34])=[CH:3][CH:2]=1

Participants

7

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 13005707Ethyl 2-(hydroxymethyl)cyclopropanecarboxylate2×HCID 584825301-(biphenyl-4-ylmethyl)-4,6-difluoro-5-iodo-2-(methylsulfonyl)-1H-benzimidazole2×

Product 1

HCID 67409526Ethyl 2-({[1-(biphenyl-4-ylmethyl)-4,6-difluoro-5-iodo-1H-benzimidazol-2-yl]oxy}methyl)cyclopropanecarboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1-(biphenyl-4-ylmethyl)-4,6-difluoro-5-iodo-2-(methylsulfonyl)-1H-benzimidazole (Intermediate 5, 0.500 g, 0.954 mmol) and 2-hydroxymethyl-cyclopropanecarboxylic acid ethyl ester (Intermediate 10, 0.550 g, 3.81 mmol) in 3.2 mL of DMF was added DBU (0.575 mL, 3.81 mmol) dropwise via syringe. The reaction was heated at 80° C. for 2 h, and then diluted with EtOAc and H2O. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The resulting crude residue was purified on silica gel (eluted 2-15% then 15-20% EtOAc/hexanes: gradient elution) to furnish the desired product. LCMS: calculated for C27H23F2IN2O3 588.38, observed m/e 588.9 (M+H)+ (Rt 2.51/4 min).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with EtOAc
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting crude residue was purified on silica gel (
  8. washeluted 2-15%
  9. wash15-20% EtOAc/hexanes: gradient elution)

Sources & evidence

ORD record
ord-6dd66103cc324a6ca8cdde952822eeb7
Source dataset
uspto-grants-2014_11
Patent number
US08895596B2

Linked notes

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