4-Fluorobenzoyl chloride → Ethyl 2-(4-fluorobenzamido)-4-(4-chlorophenyl)thiophene-3-carboxylate

HRID 2383969ノート

反応式

HRID 2383969 の反応式
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8].[F:19][C:20]1[CH:28]=[CH:27][C:23]([C:24](Cl)=[O:25])=[CH:22][CH:21]=1>C1COCC1.[OH-].[Na+].C(OCC)(=O)C>[F:19][C:20]1[CH:28]=[CH:27][C:23]([C:24]([NH:1][C:2]2[S:3][CH:4]=[C:5]([C:12]3[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=3)[C:6]=2[C:7]([O:9][CH2:10][CH3:11])=[O:8])=[O:25])=[CH:22][CH:21]=1

参加物

6

反応物 2

HCID 678794-Fluorobenzoyl chlorideHCID 616598Ethyl 2-amino-4-(4-chlorophenyl)thiophene-3-carboxylate

生成物 1

HCID 1724388Ethyl 2-(4-fluorobenzamido)-4-(4-chlorophenyl)thiophene-3-carboxylate

試薬・触媒・溶媒 3

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒HCID 14798Sodium Hydroxide溶媒

実験手順

Ethyl cyanoacetate (5 mmol), and p-chloro-acetophenone (5 mmol) are dissolved in toluene (5 mL). Morpholine (5 mmol) is added followed by activated molecular sieves (4A). The reaction is stirred at 80° C. for 12 hours. The reaction is cooled to room temperature, filtered and concentrated. The residue is taken up in toluene (5 mL), ethanol (5 mL) and sulfur is added (0.16 g; 5 mmol). The reaction mixture is heated with mixing at 70° C. for 12 hours. The reaction is cooled to room temperature and the solvents are evaporated. The residue is purified by HPLC to provide ethyl 2-amino-4-(4-chlorophenyl)-thiophene-3-carboxylate. Ethyl 2-amino-4-(4-chlorophenyl)-thiophene-3-carboxylate (5 mmol) is treated with 4-fluorobenzoyl chloride (5 mmol) in THF (10 mL). The reaction is stirred at room temperature for 10 hours. The reaction is diluted with 1N NaOH (10 mL) and ethyl acetate (15 mL). The layers are separated, the organic layer is dried with anhydrous sodium sulfate, filtered and concentrated. The residue is purified by flash chromatography to provide ethyl 2-(4-fluorobenzamido)-4-(4-chlorophenyl)thiophene-3-carboxylate. Ethyl 2-(fluorobenzamido)-4-(4-chlorophenyl)thiophene-3-carboxylate is hydrolyzed under a variety of conditions (e.g. LiOH, water; LiOH, H2O2, water; or NaOH, water) to provide 2-(4-fluorobenzamido)-4-(4-chlorophenyl)thiophene-3-carboxylic acid.

後処理

  1. customThe layers are separated
  2. dry with materialthe organic layer is dried with anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by flash chromatography

出典と根拠

ORDレコード
ord-a37dbe83343d4dd894c51e4e750147b5
出典データセット
uspto-grants-2012_09
特許番号
US08263641B2

反応ノート

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