Ethyl Acetate → 4-Chloro-1-(2-cyclopropyl-1-methyl-1h-benzimidazol-6-yl)-2(1h)-pyridinone

HRID 2203085Notes

Reaction equation

[CH:1]1([C:4]2[N:8]([CH3:9])[C:7]3[CH:10]=[C:11]([N:14]4[CH:19]=[CH:18][C:17](O)=[CH:16][C:15]4=[O:21])[CH:12]=[CH:13][C:6]=3[N:5]=2)[CH2:3][CH2:2]1.P(Cl)(Cl)([Cl:24])=O.CCOC(C)=O>CN(C=O)C>[Cl:24][C:17]1[CH:18]=[CH:19][N:14]([C:11]2[CH:12]=[CH:13][C:6]3[N:5]=[C:4]([CH:1]4[CH2:3][CH2:2]4)[N:8]([CH3:9])[C:7]=3[CH:10]=2)[C:15](=[O:21])[CH:16]=1

Participants

Conditions

Temperature: 47.5 °C

Procedure

To a suspension of 1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one (75 g) in DMF (1.3 L) was added phosphorus oxychloride (29.8 ml) at room temperature, and the mixture was stirred at 45-50° C. under Ar atmosphere for 26 h. The mixture was poured into EtOAc (1.5 L), and washed with saturated NaHCO3 solution (1.5 L). The organic layer was separated, and aqueous layer was extracted with EtOAc (2.0 L) two times. The combined organic layer was washed with brine (1.0 L), dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in EtOAc/THF (1/1, 700 ml), and NH silica gel (100 g) was added to the solution. The mixture was filtered through a plug of NH silica gel (500 g) with EtOAc as an eluent to give the title compound (47.0 g) as a pale yellow solid.

Workup

washwashed with saturated NaHCO3 solution (1.5 L)
customThe organic layer was separated
extractionaqueous layer was extracted with EtOAc (2.0 L) two times
washThe combined organic layer was washed with brine (1.0 L)
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
dissolutionThe residue was dissolved in EtOAc/THF (1/1, 700 ml)
additionNH silica gel (100 g) was added to the solution
filtrationThe mixture was filtered through a plug of NH silica gel (500 g) with EtOAc as an eluent

Sources & evidence

ORD record: ord-ea4c6e18e73b4f119bcc4fc15b3a8b45
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365540B2

Reaction notes

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