Sodium Hydroxide → HCID 178519706, compound

HRID 547669Notes

Reaction equation

HRID 547669 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:13][C:14]2[CH:22]=[CH:21][C:17]3[NH:18][CH:19]=[N:20][C:16]=3[CH:15]=2)[CH:5]=[CH:6][C:7]=1[CH:8]1OCC[O:9]1.[OH-].[Na+]>CC(C)=O.O.C(OCC)(=O)C>[NH:18]1[C:17]2[CH:21]=[CH:22][C:14]([O:13][C:4]3[CH:5]=[CH:6][C:7]([CH:8]=[O:9])=[C:2]([Cl:1])[CH:3]=3)=[CH:15][C:16]=2[N:20]=[CH:19]1

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 178478254HCID 178478254, compound

Product 1

HCID 178519706HCID 178519706, compound

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-{[3-Chloro-4-(1,3-dioxolan-2-yl)phenyl]oxy}-1H-benzimidazole (1.41 g) was dissolved in approximately 15 mL of acetone and heated at reflux over 3 days with 25 mg of p-tosic acid. An additional 50 mg of p-tosic acid was added and the reaction was heated at 80 degrees Centigrade for an additional 6 hours. The reaction was allowed to cool to room temperature, diluted with water and ethyl acetate, made basic with 10 N NaOH and extracted twice with ethyl acetate. The organic layer was washed with brine and 1N NaOH, dried over MgSO4 and concentrated. The residue was dissolved and stirred in neat trifluoroacetic acid overnight. The reaction was concentrated and purified by silica gel column chromatography (0-10% gradient of methanolic 2N NH3/CH2Cl2). The fractions were concentrated and the residue was purified by preparative HPLC to give 4-(1H-benzimidazol-5-yloxy)-2-chlorobenzaldehyde, which was ultimately used to prepare Examples Nos. 73 and 74.

Workup

  1. temperatureheated
  2. temperaturethe reaction was heated at 80 degrees Centigrade for an additional 6 hours
  3. extractionextracted twice with ethyl acetate
  4. washThe organic layer was washed with brine and 1N NaOH
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved
  8. concentrationThe reaction was concentrated
  9. custompurified by silica gel column chromatography (0-10% gradient of methanolic 2N NH3/CH2Cl2)
  10. concentrationThe fractions were concentrated
  11. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-83e17c5ffb8349afa4104b3398280eb2
Source dataset
uspto-grants-2011_05
Patent number
US07939528B2

Reaction notes

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