Hydrochloric Acid → 1-[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazol-5-yl]-2-hydroxy-ethanone

HRID 216563Notes

Reaction equation

HRID 216563 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:20](=[O:26])[CH2:21][O:22]COC)=[CH:11][C:12]3[N:16]([CH3:17])[CH:15]=[N:14][C:13]=3[C:18]=2[F:19])=[C:4]([Cl:27])[CH:3]=1.Cl.CO.C([O-])(O)=O.[Na+]>CCOC(C)=O.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:20](=[O:26])[CH2:21][OH:22])=[CH:11][C:12]3[N:16]([CH3:17])[CH:15]=[N:14][C:13]=3[C:18]=2[F:19])=[C:4]([Cl:27])[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 516892Sodium BicarbonateHCID 211141721-[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazol-5-yl]-2-methoxymethoxy-ethanone

Product 1

HCID 102378741-[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazol-5-yl]-2-hydroxy-ethanoneYield 54%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1-[6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazol-5-yl]-2-methoxymethoxy-ethanone 10j (15 mg, 0.033 mmol), 10% aqueous HCl (0.3 mL), methanol (0.01 mL), and water (0.05 mL) is stirred for 3 days at room temperature. The reaction mixture is neutralized with saturated aqueous NaHCO3, and diluted with EtOAc. The organic layer is washed with brine, dried over MgSO4, filtered, concentrated in vacuo, and purified by flash chromatography (1.5% MeOH in CH2Cl2) to afford the desired product (7.3 mg, 54%): MS APCI (+) m/z 412, 414 (M+, Br pattern) detected; 1H NMR (400 MHz, acetone-d6) δ 8.64 (s, 1H), 8.34 (s, 1H), 8.16 (s, 1H), 7.58 (d, 1H), 7.31 (dd, 1H), 6.59 (dd, 1H), 4.94 (s, 2H), 4.06 (s, 3H); 19F NMR (376 MHz, acetone-d6) −132.45 (s, 1F).

Workup

  1. washThe organic layer is washed with brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. custompurified by flash chromatography (1.5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-1c8eb87fce904079862af4c7b4fcd823
Source dataset
uspto-grants-2012_06
Patent number
US08193230B2

Reaction notes

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