Chloromethyl ethyl ether → 1-[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazol-5-yl]-2-ethoxy-ethanol

HRID 1176903Notes

Reaction equation

HRID 1176903 reaction equation
C(C1C=CC(C2C=CC(C(C)(C)C)=CC=2)=CC=1)(C)(C)C.[CH2:21]([O:23][CH2:24]Cl)[CH3:22].[Br:26][C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:34]2[C:35]([CH:44]=[O:45])=[CH:36][C:37]3[NH:41][CH:40]=[N:39][C:38]=3[C:42]=2[F:43])=[C:29]([Cl:46])[CH:28]=1>C1COCC1>[Br:26][C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:34]2[C:35]([CH:44]([OH:45])[CH2:24][O:23][CH2:21][CH3:22])=[CH:36][C:37]3[NH:41][CH:40]=[N:39][C:38]=3[C:42]=2[F:43])=[C:29]([Cl:46])[CH:28]=1

Participants

5

Reactant 3

HCID 18523Chloromethyl ethyl etherHCID 741954,4'-Bis(1,1-dimethylethyl)-1,1'-biphenylHCID 112456086-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehyde

Product 1

HCID 211141641-[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazol-5-yl]-2-ethoxy-ethanolYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of lithiomethyl ethyl in THF (6 mL) (prepared from 4,4′-di-tert-butylbiphenyl (5.85 mg, 2.20 mmol). Li (18 mg, 2.59 mmol), and EtOCH2Cl (0.20 mL, 2.05 mmol) by the procedure reported in Tetrahedron 1996, 52, 1943) is added a solution of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehyde 10f (29 mg, 0.080 mmol) in THF (1 mL) at −78° C. The resulting solution is stirred for 1 hour and then quenched with saturated aqueous NH4Cl at −78° C., warmed to room temperature, and extracted with EtOAc. The organic layer is washed with brine, dried over MgSO4, filtered, concentrated in vacuo, and purified by flash chromotography (100% CH2Cl2 to 3% to 5% MeOH in CH2 Cl2) to give the desired product (15 mg, 44%): MS APCI (+) m/z 428, 430 (M+, Br pattern) detected.

Workup

  1. customquenched with saturated aqueous NH4Cl at −78° C.
  2. extractionextracted with EtOAc
  3. washThe organic layer is washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified by flash chromotography (100% CH2Cl2 to 3% to 5% MeOH in CH2 Cl2)

Sources & evidence

ORD record
ord-774bdb3ba3024233b0360a2174ad27fa
Source dataset
uspto-grants-2010_11
Patent number
US07842816B2

Reaction notes

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