[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazol-5-yl]-methanol → 6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehyde

HRID 216470Notes

Reaction equation

HRID 216470 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([CH2:19][OH:20])=[CH:11][C:12]3[NH:16][CH:15]=[N:14][C:13]=3[C:17]=2[F:18])=[C:4]([Cl:21])[CH:3]=1>O1CCCC1.CC(C)=O.O=[Mn]=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([CH:19]=[O:20])=[CH:11][C:12]3[NH:16][CH:15]=[N:14][C:13]=3[C:17]=2[F:18])=[C:4]([Cl:21])[CH:3]=1

Participants

4

Reactant 1

HCID 11428680[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazol-5-yl]-methanol

Product 1

HCID 112456086-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehydeYield 85.2%

Reagents, catalysts & solvents 2

HCID 14801Manganese dioxideCatalystHCID 22559816Acetone tetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazol-5-yl]-methanol 10e (0.96 g, 2.58 mmol) is dissolved in tetrahydrofuran/acetone (1:1, 15 mL), and MnO2 (2.24 g, 25.8 mmol) is added. The reaction mixture is stirred at 50° C. for 10 hours under N2. The reaction mixture is filtered through silica gel and eluted with methylene chloride/methanol (10:1, 1 L). The filtrate is concentrated under reduced pressure to a small volume and then filtered through an Acrodisc syringe filter to remove small amounts of MnO2 that passed through the silica gel. The filtrate is concentrated under reduced pressure and the residue is purified by flash column chromatography (eluting with 20:1 methylene chloride:methanol) to yield 0.81 g (85%) of the pure desired product as a bright yellow solid. MS ESI (+) m/z 368, 370 (M+, Br pattern) detected.

Workup

  1. filtrationThe reaction mixture is filtered through silica gel
  2. washeluted with methylene chloride/methanol (10:1, 1 L)
  3. concentrationThe filtrate is concentrated under reduced pressure to a small volume
  4. filtrationfiltered through an Acrodisc syringe
  5. filtrationfilter
  6. customto remove small amounts of MnO2 that
  7. concentrationThe filtrate is concentrated under reduced pressure
  8. customthe residue is purified by flash column chromatography (eluting with 20:1 methylene chloride:methanol)

Sources & evidence

ORD record
ord-bafce661e30244d0b1c663acf6294f94
Source dataset
uspto-grants-2012_06
Patent number
US08193229B2

Reaction notes

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