Ethyl 3-hydroxycyclopentanecarboxylate → Ethyl 3-{[5-(biphenyl-4-yl)-6-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-2-yl]oxy}cyclopentanecarboxylate

HRID 340779Notes

Reaction equation

HRID 340779 reaction equation
[C:1]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:6]=[CH:5][C:4]([C:7]2[C:27]([Cl:28])=[CH:26][C:10]3[N:11]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:12](S(C)(=O)=O)=[N:13][C:9]=3[CH:8]=2)=[CH:3][CH:2]=1.[OH:35][CH:36]1[CH2:40][CH2:39][CH:38]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:37]1>CN(C=O)C.CCOC(C)=O>[C:1]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:6]=[CH:5][C:4]([C:7]2[C:27]([Cl:28])=[CH:26][C:10]3[N:11]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:12]([O:35][CH:36]4[CH2:40][CH2:39][CH:38]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:37]4)=[N:13][C:9]=3[CH:8]=2)=[CH:3][CH:2]=1

Participants

5

Reactant 2

HCID 53407781Ethyl 3-hydroxycyclopentanecarboxylate2×HCID 583871305-biphenyl-4-yl-6-chloro-2-(methylsulfonyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole2×

Product 1

HCID 71074041Ethyl 3-{[5-(biphenyl-4-yl)-6-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-2-yl]oxy}cyclopentanecarboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-(biphenyl-4-yl)-6-chloro-2-(methylsulfonyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole (Intermediate 3, 0.350 g, 0.682 mmol) and ethyl 3-hydroxycyclopentanecarboxylate (Intermediate 9, 0.647 mL, 4.09 mmol) in 2.3 mL DMF was added DSU (0.514 mL. 3.41 mmol) dropwise via syringe. The reaction was heated overnight at 80° C., then diluted with EtOAc, and washed with H2O and brine. The aqueous layer was further extracted with EtOAc, and the combined organic layers were dried over Na2SO4, filtered, and concentrated. Purification of the resulting residue by preparative TLC (25% EtOAc/hexanes) furnished the desired compound as a pale yellow oil. LCMS: calculated for C33H39ClN2O4Si 591.21, observed m/e 591.04 M+ (Rt 3.06/4 min).

Workup

  1. washwashed with H2O and brine
  2. extractionThe aqueous layer was further extracted with EtOAc
  3. dry with materialthe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the resulting residue by preparative TLC (25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-2463233a0be0452b9c9dbb6ac2b83eb3
Source dataset
uspto-grants-2014_11
Patent number
US08895596B2

Reaction notes

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