Dimethylformamide → 1-Isopropylsulfonyl-2-amino-6-formylbenzimidazole

HRID 2252016Notes

Reaction equation

C1([Li])C=CC=CC=1.[CH:8]([S:11]([N:14]1[C:18]2[CH:19]=[C:20](I)[CH:21]=[CH:22][C:17]=2[N:16]=[C:15]1[NH2:24])(=[O:13])=[O:12])([CH3:10])[CH3:9].C([Li])(C)(C)C.CN(C)[CH:32]=[O:33]>O1CCCC1>[CH:8]([S:11]([N:14]1[C:18]2[CH:19]=[C:20]([CH:32]=[O:33])[CH:21]=[CH:22][C:17]=2[N:16]=[C:15]1[NH2:24])(=[O:13])=[O:12])([CH3:10])[CH3:9]

Participants

Conditions

Temperature: 0 °C

Procedure

Add phenyllithium (750 mL, 1.8 M in cyclohexane/ether, 70/30) over 1 hour to a solution of 1-isopropylsulfonyl-2-amino-6-iodobenzimidazole (150 g, 0.41 mol) in tetra-hydrofuran (5.6 L) at −76° C. Stir for 15 minutes and then add tert-butyllithium (750 ml, 1.7 M in pentane). After 1 hour add dimethylformamide (250 mL) slowly over one hour and then warm to 0° C. Quench by pouring the reaction mixture into a mixture of cold saturated aqueous ammonium chloride (500 g, 5 L) and concentrated hydrochloric acid (300 mL). Separate the layers, wash the organic phase with water and then concentrate under reduced pressure. Slurry the residue in methanol (500 mL), filter the yellow precipitate, and dry to provide 85 g (76%) of the title compound.

Workup

customQuench
additionby pouring the reaction mixture
additioninto a mixture of cold saturated aqueous ammonium chloride (500 g, 5 L) and concentrated hydrochloric acid (300 mL)
customSeparate the layers
washwash the organic phase with water
concentrationconcentrate under reduced pressure
filtrationfilter the yellow precipitate
customdry

Sources & evidence

ORD record: ord-5aecafb1e45047e6b155a77f60236677
Source dataset: uspto-grants-2008_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07320995B2

Reaction notes

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