Potassium Carbonate → Ethyl 3-{[5-(biphenyl-4-yl)-1-(biphenyl-4-ylmethyl)-4,6-difluoro-1H-benzimidazol-2-yl]oxy}cyclobutanecarboxylate

HRID 340795Notes

Reaction equation

HRID 340795 reaction equation
[C:1]1([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:6]=[CH:5][C:4]([CH2:7][N:8]2[C:12]3[CH:13]=[C:14]([F:19])[C:15](I)=[C:16]([F:17])[C:11]=3[N:10]=[C:9]2[O:20][CH:21]2[CH2:24][CH:23]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:22]2)=[CH:3][CH:2]=1.B(O)(O)[C:37]1[CH:38]=[CH:39][C:40]([C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)=[CH:41][CH:42]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:40]1([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:41]=[CH:42][C:37]([C:15]2[C:14]([F:19])=[CH:13][C:12]3[N:8]([CH2:7][C:4]4[CH:5]=[CH:6][C:1]([C:30]5[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=5)=[CH:2][CH:3]=4)[C:9]([O:20][CH:21]4[CH2:22][CH:23]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:24]4)=[N:10][C:11]=3[C:16]=2[F:17])=[CH:38][CH:39]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 1512531,1'-Biphenyl-4-yl-boronic acidHCID 67408998Ethyl 3-{[1-(biphenyl-4-ylmethyl)-4,6-difluoro-5-iodo-1H-benzimidazol-2-yl]oxy}cyclobutanecarboxylate

Product 1

HCID 67407044Ethyl 3-{[5-(biphenyl-4-yl)-1-(biphenyl-4-ylmethyl)-4,6-difluoro-1H-benzimidazol-2-yl]oxy}cyclobutanecarboxylate

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A solution of ethyl 3-{[1-(biphenyl-4-ylmethyl)-4,6-difluoro-5-iodo-1H-benzimidazol-2-yl]oxy}cyclobutanecarboxylate (0.350 g, 0.595 mmol), biphenylboronic acid (0.130 g, 0.654 mmol), and Pd(PPh3)4 (0.027 g, 0.024 mmol) in 6 mL of DMF was treated with a 1 M solution of K2CO3 (1.20 mL). The resulting yellow solution was heated at 120° C. for 45 min, 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. Purification of the resulting residue by flash chromatography (0-15% then 15-20% then 20% EtOAc/hexanes) provided the desired product as a white solid. LCMS: calculated for C39H32F2N2O3 614.68, observed ink 615.1 (M+H)+ (Rt 2.79/4 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. customPurification of the resulting residue by flash chromatography (0-15%

Sources & evidence

ORD record
ord-facc36a78da949ab8a6c2d65b96159bf
Source dataset
uspto-grants-2014_11
Patent number
US08895596B2

Reaction notes

Loading…