Tetrabutylammonium Fluoride → HCID 53372243, compound

HRID 340778Notes

Reaction equation

HRID 340778 reaction equation
[C:1]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:6]=[CH:5][C:4]([C:7]2[C:40]([Cl:41])=[CH:39][C:10]3[N:11](COCC[Si](C)(C)C)[C:12]([O:14][CH:15]4[CH2:20][CH2:19][CH2:18][CH:17]([C:21]([O:23]CC5C=CC=CC=5)=[O:22])[CH2:16]4)=[N:13][C:9]=3[CH:8]=2)=[CH:3][CH:2]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.CCOC(C)=O>[C:1]1([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH:2]=[CH:3][C:4]([C:7]2[C:40]([Cl:41])=[CH:39][C:10]3[NH:11][C:12]([O:14][CH:15]4[CH2:20][CH2:19][CH2:18][CH:17]([C:21]([OH:23])=[O:22])[CH2:16]4)=[N:13][C:9]=3[CH:8]=2)=[CH:5][CH:6]=1

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 71074161HCID 71074161, compound

Product 1

HCID 53372243HCID 53372243, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of benzyl 3-{[5-(biphenyl-4-yl)-6-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-2-yl]oxy}cyclohexanecarboxylate (isomer A from Step A, 0.075 g, 0.112 mmol) in 1.1 mL of THF was added TBAF (0.675 mL, 0.675 mmol) dropwise via syringe. The reaction was heated at 80° C. for 16 h, and then diluted with EtOAc (50 mL) and washed with 2 N HCl (2×20 mL). The organic layer was washed with H2O and brine, dried over Na2SO4, filtered, and concentrated. Purification of the resulting residue by reverse phase Gilson™ HPLC (30-100% MeCN/H2O) afforded the title compound as a white solid. LCMS: calculated for C26H23ClN2O3 446.93, observed m/e 446.92M+ (Rt 2.19/4 min). 1H NMR (500 MHz, CD3OD): δ7.71-7.64 (m, 4H), 7.55 (brs, 1H), 7.50 (d, 2H), 7.48-7.43 (m, 2H), 7.39 (brs, 1H), 7.37-7.32 (m, 1H), 5.00-4.91 (m, 1H), 2.60-2.46 (m, 2H), 2.33-2.24 (m, 1H), 2.06-1.95 (m, 2H), 1.79-1.67 (m, 1H), 1.64-1.49 (m, 2H), 1.49-1.37 (m, 1H).

Workup

  1. washwashed with 2 N HCl (2×20 mL)
  2. washThe organic layer was washed with H2O and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the resulting residue by reverse phase Gilson™ HPLC (30-100% MeCN/H2O)

Sources & evidence

ORD record
ord-1a86e538e0484d4aa11139aaff8be0a6
Source dataset
uspto-grants-2014_11
Patent number
US08895596B2

Reaction notes

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