Methyl 6-((4-bromo-2-chlorophenyl)amino)-7-fluoro-1H-benzo[d]imidazole-5-carboxylate → [6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazol-5-yl]-methanol

HRID 216469ノート

反応式

HRID 216469 の反応式
C[O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=2[Cl:22])=[C:12]([F:23])[C:8]2[N:9]=[CH:10][NH:11][C:7]=2[CH:6]=1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[Br:21][C:18]1[CH:19]=[CH:20][C:15]([NH:14][C:13]2[C:5]([CH2:3][OH:2])=[CH:6][C:7]3[NH:11][CH:10]=[N:9][C:8]=3[C:12]=2[F:23])=[C:16]([Cl:22])[CH:17]=1

参加物

4

反応物 2

HCID 11749905Methyl 6-((4-bromo-2-chlorophenyl)amino)-7-fluoro-1H-benzo[d]imidazole-5-carboxylateHCID 21226445Aluminium lithium hydride

生成物 1

HCID 11428680[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazol-5-yl]-methanol収率 100%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester 8b (1.06 g, 2.65 mmol) is suspended in tetrahydrofuran (25 mL) and cooled to −78° C. Lithium aluminum hydride (8.03 mL, 8.03 mmol, 1M solution in tetrahydrofuran) is added dropwise to the reaction mixture. After stirring for 10 minutes at −78° C., the reaction mixture is warmed to 0° C. and becomes a homogeneous solution. The reaction mixture is stirred for 5 minutes at 0° C. and then cooled again to −78° C. The reaction mixture is quenched with MeOH, diluted with Rochelle's salt, warmed to room temperature and stirred for 1 hour. The reaction mixture is then poured into a separatory funnel, diluted with ethyl acetate, and the layers separated. The aqueous phase is extracted with ethyl acetate. The combined ethyl acetate layers are dried (Na2SO4) and concentrated under reduced pressure to yield 0.98 g (100%) of the pure desired product as a pale yellow solid. MS ESI (+) m/z 370, 372 (M+, Br pattern) detected.

後処理

  1. temperaturethe reaction mixture is warmed to 0° C.
  2. stirringThe reaction mixture is stirred for 5 minutes at 0° C.
  3. temperaturecooled again to −78° C
  4. customThe reaction mixture is quenched with MeOH
  5. additiondiluted with Rochelle's salt
  6. temperaturewarmed to room temperature
  7. stirringstirred for 1 hour
  8. additionThe reaction mixture is then poured into a separatory funnel
  9. additiondiluted with ethyl acetate
  10. customthe layers separated
  11. extractionThe aqueous phase is extracted with ethyl acetate
  12. dry with materialThe combined ethyl acetate layers are dried (Na2SO4)
  13. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-fc408df0c75141eaaa14a9583d2afab2
出典データセット
uspto-grants-2012_06
特許番号
US08193229B2

反応ノート

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