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

HRID 32015

反応式

HRID 32015 の反応式
C(OC[Li])C.C(C1C=CC(C2C=CC(C(C)(C)C)=CC=2)=CC=1)(C)(C)C.[CH2:26]([O:28][CH2:29]Cl)[CH3:27].[Br:31][C:32]1[CH:37]=[CH:36][C:35]([NH:38][C:39]2[C:40]([CH:49]=[O:50])=[CH:41][C:42]3[NH:46][CH:45]=[N:44][C:43]=3[C:47]=2[F:48])=[C:34]([Cl:51])[CH:33]=1>C1COCC1>[Br:31][C:32]1[CH:37]=[CH:36][C:35]([NH:38][C:39]2[C:40]([CH:49]([OH:50])[CH2:29][O:28][CH2:26][CH3:27])=[CH:41][C:42]3[NH:46][CH:45]=[N:44][C:43]=3[C:47]=2[F:48])=[C:34]([Cl:51])[CH:33]=1

参加物

6

反応物 4

HCID 18523Chloromethyl ethyl etherHCID 741954,4'-Bis(1,1-dimethylethyl)-1,1'-biphenylHCID 112456086-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehydeHCID 178506881HCID 178506881、化合物

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of lithiomethyl ethyl ether in THF (6 mL) (prepared from 4,4′-di-tert-butylbiphenyl (585 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, 1643) 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 chromatography (100% CH2Cl2 to 3% to 5% MeOH in CH2Cl2) to give the desired product (15 mg, 44%): MS APCI (+) m/z 428, 430 (M+, Br pattern) detected.

後処理

  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 chromatography (100% CH2Cl2 to 3% to 5% MeOH in CH2Cl2)

出典と根拠

ORDレコード
ord-9a171fb551a142f0985d8089be921df5
出典データセット
uspto-grants-2008_09
特許番号
US07425637B2

関連ノート

読み込み中…