Aminoisobutyric acid → 2-((4-Carbamoyl-3-fluorophenyl)amino)-2-methylpropanoic acid

HRID 38753

反応式

HRID 38753 の反応式
Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[C:4]([F:11])[CH:3]=1.[NH2:12][C:13]([CH3:18])([CH3:17])[C:14]([OH:16])=[O:15].C([O-])([O-])=O.[K+].[K+].C(C1CCCCC1=O)(=O)C>CN(C=O)C.O.[Cu]I>[C:6]([C:5]1[CH:9]=[CH:10][C:2]([NH:12][C:13]([CH3:18])([CH3:17])[C:14]([OH:16])=[O:15])=[CH:3][C:4]=1[F:11])(=[O:7])[NH2:8]

参加物

8

反応物 4

HCID 6119Aminoisobutyric acidHCID 11430Potassium CarbonateHCID 134002-AcetylcyclohexanoneHCID 27733314-Bromo-2-fluorobenzamide

生成物 1

HCID 666179022-((4-Carbamoyl-3-fluorophenyl)amino)-2-methylpropanoic acid

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 962Water溶媒2 回HCID 6228Dimethylformamide溶媒

反応条件

温度
97.5 °C

実験手順

4-Bromo-2-fluorobenzamide (0.5 g, 2.29 mmol), 2 aminoisobutyric acid (0.354 g, 3.54 mmol), CuI (87 mg, 0.458 mmol), and K2CO3 (0.790 g, 5.72 mmol) were mixed in DMF (5 mL). H2O (0.5 mL) and TEA (11 mg, 0.1 mmol) were added followed by 2-acetyl cyclohexanone (60 mg, 0.428 mmol).The reaction mixture was heated to 95-100° C. for 48 h. The reaction mixture was diluted with H2O (20 mL) and the aqueous layer was washed with ethyl acetate (20 mL). The aqueous layer was acidified with 1M citric acid to pH 4 and the product was extracted with ethyl acetate (20 mL×3). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain the product. 1H NMR (DMSO, Freebase): δ (ppm) 7.55-7.45 (t, 1H), 7.20 (bs, 1H), 7.05 (bs, 1H), 6.80 (bs, 1H), 6.35-6.30 (d, 1H), 6.18-6.10 (d, 1H), 1.42 (s, 6H).

後処理

  1. washthe aqueous layer was washed with ethyl acetate (20 mL)
  2. extractionthe product was extracted with ethyl acetate (20 mL×3)
  3. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto obtain the product

出典と根拠

ORDレコード
ord-793f1188cf4d41e1a8718bd601062328
出典データセット
uspto-grants-2013_09
特許番号
US08524755B2

関連ノート

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