Tetrabutylammonium Fluoride → HCID 45256867, compound

HRID 1945302Notes

Reaction equation

HRID 1945302 reaction equation
CCCC[N+](CCCC)(CCCC)CCCC.[F-].[Cl:19][C:20]1[C:21]([C:49]2[CH:54]=[CH:53][C:52]([C:55]3([CH2:58][OH:59])[CH2:57][CH2:56]3)=[CH:51][CH:50]=2)=[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>O1CCOCC1>[Cl:19][C:20]1[C:21]([C:49]2[CH:54]=[CH:53][C:52]([C:55]3([CH2:58][OH:59])[CH2:56][CH2:57]3)=[CH:51][CH:50]=2)=[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

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 68659473HCID 68659473, compound

Product 1

HCID 45256867HCID 45256867, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

TBAF (1M in THF) (0.35 mL, 0.35 mmol) was added to a solution of methyl 5-[(6-chloro-5-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-2-yl)oxy]-2-methylbenzoate (275 mg, 0.464 mmol) in dioxane (5 mL) and reaction mixture was heated at 80° C. The volatiles were removed. The resulting crude residue was dissolved in MeOH (2 ml) and 2.5 N aqueous NaOH (2 mL) and stirred at 50° C. for 1 h. Volatiles were removed and the residue was partitioned between EtOAc and water. The aqueous layer was acidified to pH=1 with 2 N aqueous HCl, and extracted with EtOAc. Combined organic layers were dried (MgSO4), filtered and concentrated. Purification by reverse phase HPLC eluting with 10-100% acetonitrile:water afforded the title compound. LC-MS calculated for C25H21ClN2O4 448.12, observed m/e 448.7 (M+H)+. Rt: 1.81/4 min. 1H NMR (500 MHz, CD3OD): δ 7.85 (s, 1H), 7.50 (s, 1H), 7.40-7.45 (m, 4H), 7.35 (d, 2H), 7.30 (s, 1H), 3.65 (s, 2H), 2.61 (s, 3H), 0.85-0.95 (q, 4H).

Workup

  1. customThe volatiles were removed
  2. dissolutionThe resulting crude residue was dissolved in MeOH (2 ml)
  3. customVolatiles were removed
  4. customthe residue was partitioned between EtOAc and water
  5. extractionextracted with EtOAc
  6. dry with materialCombined organic layers were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by reverse phase HPLC
  10. washeluting with 10-100% acetonitrile

Sources & evidence

ORD record
ord-80b362eb625346dd97e24f07d6c365b7
Source dataset
uspto-grants-2013_03
Patent number
US08394969B2

Reaction notes

Loading…