N-bromobutanimide → HCID 178497004、化合物

HRID 216424ノート

反応式

HRID 216424 の反応式
[CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])=[C:12]([F:22])[C:8]2[NH:9][CH:10]=[N:11][C:7]=2[CH:6]=1)=[O:4].C1COCC1.CO.C1C(=O)N([Br:37])C(=O)C1.CC1C=CC(S(O)(=O)=O)=CC=1.O>CO>[CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([Br:37])=[CH:17][C:16]=2[CH3:21])=[C:12]([F:22])[C:8]2[NH:9][CH:10]=[N:11][C:7]=2[CH:6]=1)=[O:4]

参加物

6

反応物 4

HCID 67184N-bromobutanimide2 回HCID 521998p-Toluenesulfonic acid monohydrateHCID 21899815MeOH tetrahydrofuran2 回HCID 178497005HCID 178497005、化合物

生成物 1

HCID 178497004HCID 178497004、化合物収率 79.2%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
-78 °C

実験手順

7-Fluoro-6-o-tolylamino-1H-benzoimidazole-5-carboxylic acid methyl ester 7a (2.00 g, 6.68 mmol) is suspended in 1:1 THF/MeOH (60 mL) and cooled to −78° C. under a nitrogen atmosphere. A solution of NBS (1.20 g, 6.75 mmol) in 1:1 THF/MeOH (5 mL) is added followed by a MeOH (5 mL) solution of TsOH.H2O (1.9 g, 10.0 mmol). After 30 minutes, the reaction mixture is warmed to 0° C. and then after 1 hour warmed to room temperature. After 16 hours, more NBS (0.12 g, 0.67 mmol) is added and the reaction mixture is allowed to stir for 3 hours. The reaction mixture is quenched by the addition of 10% Na2S2O4 solution. After 30 minutes, the reaction mixture is diluted with water and ethyl acetate and the layers separated. The aqueous layer is extracted with ethyl acetate. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. The recovered solid is triturated with methylene chloride to give 2.00 g (79%) pure desired product: MS APCI (+) m/z 380, 378 (M+1 Br pattern) detected.

後処理

  1. temperaturethe reaction mixture is warmed to 0° C.
  2. temperatureafter 1 hour warmed to room temperature
  3. waitAfter 16 hours
  4. customThe reaction mixture is quenched by the addition of 10% Na2S2O4 solution
  5. waitAfter 30 minutes
  6. additionthe reaction mixture is diluted with water and ethyl acetate
  7. customthe layers separated
  8. extractionThe aqueous layer is extracted with ethyl acetate
  9. dry with materialThe combined organic extracts are dried (Na2SO4)
  10. concentrationconcentrated under reduced pressure
  11. customThe recovered solid is triturated with methylene chloride

出典と根拠

ORDレコード
ord-7935da8db73540339a4c3f57d9c6b224
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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