Tetrabutylammonium Fluoride → HCID 53372242, compound

HRID 340777Notes

Reaction equation

HRID 340777 reaction equation
[C:1]1([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH:6]=[CH:5][C:4]([C:7]2[C:35]([Cl:36])=[CH:34][C:10]3[N:11](COCC[Si](C)(C)C)[C:12]([O:14][CH:15]4[CH2:20][CH2:19][CH:18]([C:21]([O:23]CC)=[O:22])[CH2:17][CH2:16]4)=[N:13][C:9]=3[CH:8]=2)=[CH:3][CH:2]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:1]1([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH:2]=[CH:3][C:4]([C:7]2[C:35]([Cl:36])=[CH:34][C:10]3[NH:11][C:12]([O:14][CH:15]4[CH2:20][CH2:19][CH:18]([C:21]([OH:23])=[O:22])[CH2:17][CH2:16]4)=[N:13][C:9]=3[CH:8]=2)=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 71073886HCID 71073886, compound

Product 1

HCID 53372242HCID 53372242, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of ethyl 4-{[5-(biphenyl-4-yl)-6-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-2-yl]oxy}cyclohexanecarboxylate (0.075 g, 0.124 mmol) in 2 mL of THF was added TBAF (0.750 mL, 0.750 mmol) dropwise via syringe. The reaction was heated at 80° C. of 2 h, and then the volatiles were removed. The resulting crude ester was dissolved in 4 mL of MeOH and treated with 1 mL of 2.5 N NaOH. The reaction was heated at 45° C. for 1.5 h, and then concentrated. The resulting residue was dissolved in H2O and acidified to pH 1 with 2 N HCl. The acidified aqueous layer was extracted with EtOAc. The combined organic layers were washed with 2 N HCl, H2O, and brine. The organic layers were dried over Na2SO4, filtered, and concentrated. Purification of the resulting residue by reverse phase Gilson™ HPLC (30-100% CH3CN/H2O) afforded the title compound as a white solid. LCMS: calculated for C26H23ClN2O3 446.93, observed m/e 446.94 M+ (Rt 2.11/4 min). 1H NMR (500 MHz, CD3OD): δ7.70-7.64 (m, 4H), 7.55 (s, 1H), 7.49 (d, 2H), 7.47-7.42 (m, 2H), 7.39 (s, 1H), 7.37-7.32 (m, 1H), 4.97-4.89 (m, 1H), 2.45-2.35 (m, 1H), 2.36-2.28 (m, 2H), 2.18-2.10 (m, 2H), 1.76-1.61 (m, 2H).

Workup

  1. customthe volatiles were removed
  2. dissolutionThe resulting crude ester was dissolved in 4 mL of MeOH
  3. additiontreated with 1 mL of 2.5 N NaOH
  4. temperatureThe reaction was heated at 45° C. for 1.5 h
  5. concentrationconcentrated
  6. dissolutionThe resulting residue was dissolved in H2O
  7. extractionThe acidified aqueous layer was extracted with EtOAc
  8. washThe combined organic layers were washed with 2 N HCl, H2O, and brine
  9. dry with materialThe organic layers were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification of the resulting residue by reverse phase Gilson™ HPLC (30-100% CH3CN/H2O)

Sources & evidence

ORD record
ord-c96c82c881f340e082fdf1ddd9ac008b
Source dataset
uspto-grants-2014_11
Patent number
US08895596B2

Reaction notes

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