Sodium Hydroxide → HCID 66835739, compound

HRID 572840Notes

Reaction equation

HRID 572840 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH2:10])[C:5]([NH2:9])=[CH:6][C:7]=1[Cl:8].C[Al](C)C.C(O[C:18](=O)[CH:19]([O:26][CH:27]1[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)C.[OH-].[Na+]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]2[NH:9][C:18]([CH:19]([O:26][CH:27]3[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[N:10][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 792974,5-Dichloro-1,2-phenylenediamineHCID 16682925TrimethylaluminumHCID 66835932HCID 66835932, compound

Product 1

HCID 66835739HCID 66835739, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Conditions

Temperature
60 °C

Procedure

A round-bottom flask is charged with 4,5-dichlorobenzene-1,2-diamine (354 mg) and toluene (2 mL); a solution of trimethylaluminum 2M in toluene (1 mL) is added dropwise. The reaction mixture is heated at 60° C. for one hour. A solution of (1-methyl-piperidin-4-yloxy)phenylacetic acid ethyl ester in toluene (1 mL) is added dropwise and heating is pursued for one hour. The reaction mixture is cooled to room-temperature and a solution of sodium hydroxide is added dropwise to pH 10. The slurry is filtered on celite, cake washed with water (4×5 mL) and ethyl acetate (4×5 mL). After decantation, the aqueous phase is extracted with ethyl acetate. The pooled organic extracts are washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue is diluted with glacial acetic acid (3 mL) and the reaction mixture is heated at reflux for one hour. Acetic acid is removed on a rotary evaporator and the residue is purified by chromatography (gradient dichloromethane/methanol/ammonia from 98/2/0 to 95/5/0.5 to give 5,6-dichloro-2-[(1-methylpiperidin-4-yloxy)phenylmethyl]-1H-benzimidazole melting at 221° C.

Workup

  1. temperatureheating
  2. temperatureThe reaction mixture is cooled to room-temperature
  3. filtrationThe slurry is filtered on celite, cake
  4. washwashed with water (4×5 mL) and ethyl acetate (4×5 mL)
  5. extractionAfter decantation, the aqueous phase is extracted with ethyl acetate
  6. washThe pooled organic extracts are washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. additionThe residue is diluted with glacial acetic acid (3 mL)
  10. temperaturethe reaction mixture is heated
  11. temperatureat reflux for one hour
  12. customAcetic acid is removed on a rotary evaporator
  13. customthe residue is purified by chromatography (gradient dichloromethane/methanol/ammonia from 98/2/0 to 95/5/0.5

Sources & evidence

ORD record
ord-df906398b42e4608a8fc3b40e8cf9838
Source dataset
uspto-grants-2015_05
Patent number
US09029357B2

Reaction notes

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