Tetrabutylammonium Fluoride → HCID 45256692, compound

HRID 1945310Notes

Reaction equation

HRID 1945310 reaction equation
CCCC[N+](CCCC)(CCCC)CCCC.[F-].[Cl:19][C:20]1[C:21]([C:49]2[CH:50]=[C:51]3[C:55](=[CH:56][C:57]=2[F:58])[N:54]([CH2:59][CH2:60][OH:61])[CH:53]=[CH:52]3)=[CH:22][C:23]2[N:27]=[C:26]([O:28][C:29]3[CH:30]=[CH:31][C:32]([CH3:39])=[C:33]([CH:38]=3)[C:34]([O:36]C)=[O:35])[N:25](COCC[Si](C)(C)C)[C:24]=2[CH:48]=1>C1COCC1.CCOC(C)=O>[Cl:19][C:20]1[C:21]([C:49]2[CH:50]=[C:51]3[C:55](=[CH:56][C:57]=2[F:58])[N:54]([CH2:59][CH2:60][OH:61])[CH:53]=[CH:52]3)=[CH:22][C:23]2[N:27]=[C:26]([O:28][C:29]3[CH:30]=[CH:31][C:32]([CH3:39])=[C:33]([CH:38]=3)[C:34]([OH:36])=[O:35])[NH:25][C:24]=2[CH:48]=1

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 68659495HCID 68659495, compound

Product 1

HCID 45256692HCID 45256692, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

TBAF (1 M in THF) (2 mL, 2 mmol) was added to a solution of methyl 5-[(6-chloro-5-[6-fluoro-1-(2-hydroxyethyl)-1H-indol-5-yl]-1-{[2-(trimethylsilyl)-ethoxy]methyl}-1H-benzimidazol-2-yl)oxy]-2-methylbenzoate in THF (2 mL). The reaction was heated at 80° C. for 3 h. Volatiles were removed and the residue was dissolved in MeOH (4 mL) and treated with 2.5 N aqueous NaOH (1.5 mL). The reaction was stirred at 45° C. for 1 h, then at rt overnight. Reaction mixture was diluted with EtOAc and washed with 1 M aqueous HCl and brine. The organic layer was dried (Na2SO4), filtered, and concentrated. Chromatography over silica eluting with 8% MeOH/DCM afforded the title compound as a beige solid. 1H NMR (500 MHz, CD3OD): δ 7.86 (d, 1H), 7.48 (s, 1H), 7.44-7.37 (m, 3H), 7.33 (s, 1 H), 7.27 (d, 1H), 7.23 (d, 1H), 6.46 (d, 1H), 4.25 (t, 2H), 3.88 (t, 2H), 2.61 (s, 3H). LC-MS: m/e 480.2 (M+H)+ (1.79 min).

Workup

  1. customVolatiles were removed
  2. dissolutionthe residue was dissolved in MeOH (4 mL)
  3. additiontreated with 2.5 N aqueous NaOH (1.5 mL)
  4. customat rt
  5. customovernight
  6. customReaction mixture
  7. washwashed with 1 M aqueous HCl and brine
  8. dry with materialThe organic layer was dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-c5b77b33f9ff4e8482954f0b16241233
Source dataset
uspto-grants-2013_03
Patent number
US08394969B2

Reaction notes

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