Acetic Acid → 2-(4-isopropyl-phenyl)-7-methoxy-1-(2-methoxy-ethyl)-1H-benzoimidazole-5-carbaldehyde

HRID 1661946Notes

Reaction equation

[OH:1][CH2:2][CH2:3][N:4]1[C:8]2[C:9]([O:15][CH3:16])=[CH:10]C(C#N)=[CH:12][C:7]=2[N:6]=[C:5]1[C:17]1[CH:22]=[CH:21][C:20]([CH:23]([CH3:25])[CH3:24])=[CH:19][CH:18]=1.[C:26]([OH:29])(=O)[CH3:27].[PH2]([O-])=O.[Na+].N1C=CC=C[CH:35]=1>O.[Ni]>[CH:23]([C:20]1[CH:21]=[CH:22][C:17]([C:5]2[N:4]([CH2:3][CH2:2][O:1][CH3:35])[C:8]3[C:9]([O:15][CH3:16])=[CH:10][C:27]([CH:26]=[O:29])=[CH:12][C:7]=3[N:6]=2)=[CH:18][CH:19]=1)([CH3:25])[CH3:24]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 7.02 g (20.1 mmol) of 1-(2-Hydroxy-ethyl)-2-(4-isopropyl-phenyl)-7-methoxy-1H-benzoimidazole-5-carbonitrile in 280 ml pyridine is added 140 ml acetic acid. After addition of a solution of 14.1 g (161 mmol) sodium hypophosphite in 140 ml water and heating to 50° C. Raney-Nickel is added in 50 mg portions (3× over 12 h) until the reaction is complete. The reaction mixtures is cooled to RT, ice/water is added and the reaction mixture is extracted with ethyl acetate (3×). The organic layer is washed with water, in vacuo and azeotroped with toluene. The residue is suspended in 100 ml CH2Cl2, filtered and washed with CH2Cl2 and ethyl acetate. The mother liquor is evaporated and purified by flash-chromatography on silica gel (hexanes/EtOAc) to give 3.78 g of colorless crystals.

Workup

customThe reaction mixtures
temperatureis cooled to RT
extractionthe reaction mixture is extracted with ethyl acetate (3×)
washThe organic layer is washed with water, in vacuo
customazeotroped with toluene
filtrationfiltered
washwashed with CH2Cl2 and ethyl acetate
customThe mother liquor is evaporated
custompurified by flash-chromatography on silica gel (hexanes/EtOAc)

Sources & evidence

ORD record: ord-77fcf9c3ea4b4a4080167a39e99f0b9a
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08030497B2

Reaction notes

Loading…