p-Toluenesulfonic acid monohydrate → 6-Bromo-5-(2,4-difluorophenoxy)-1H-benzimidazole

HRID 629307Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([NH2:18])[C:5]([NH2:17])=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[F:16].[CH:19]([O-])([O-])OCC.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCCC1>[Br:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[F:16])=[CH:6][C:5]2[N:17]=[CH:19][NH:18][C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 4-bromo-5-(2,4-difluorophenoxy)benzene-1,2-diamine (0.090 g, 0.28 mmol) in tetrahydrofuran (1.1 mL) was treated with ethyl orthoformate (0.142 mL, 0.857 mmol) followed by p-toluenesulfonic acid monohydrate (0.005 g, 0.03 mmol) and stirred at 50° C. for 1 h. The reaction mixture was concentrated and diluted with ethyl acetate and saturated sodium bicarbonate. The organic layer was separated and washed with brine, dried with magnesium sulfate, filtered, and concentrated to give a crude oil. Purification by flash column chromatography (100% hexanes to 100% EtOAc) gave the desired product (69 mg, 74%). LCMS calculated for C13H8BrF2N2O (M+H)+: m/z=325.0, 327.0. found: 325.0, 327.0.

Workup

concentrationThe reaction mixture was concentrated
additiondiluted with ethyl acetate and saturated sodium bicarbonate
customThe organic layer was separated
washwashed with brine
dry with materialdried with magnesium sulfate
filtrationfiltered
concentrationconcentrated
customto give a crude oil
customPurification by flash column chromatography (100% hexanes to 100% EtOAc)

Sources & evidence

ORD record: ord-6d300c234c854629bd1c6dbd695af6fb
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315501B2

Reaction notes

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