Aminoisobutyric acid → 4-(2-Carboxypropan-2-ylamino)-2-fluorobenzoic acid

HRID 705415ノート

反応式

HRID 705415 の反応式
Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH: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.[Cu]I.O>[C:14]([C:13]([NH:12][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([F:11])[CH:3]=1)([CH3:18])[CH3:17])([OH:16])=[O:15]

参加物

8

反応物 4

HCID 6119Aminoisobutyric acidHCID 11430Potassium CarbonateHCID 134002-AcetylcyclohexanoneHCID 3026814-Bromo-2-fluorobenzoic acid

生成物 1

HCID 673955034-(2-Carboxypropan-2-ylamino)-2-fluorobenzoic acid収率 72.7%

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
90 °C

実験手順

4-Bromo-2-fluorobenzoic acid (20 g, 91.3 mmol), 2-aminoisobutyric acid (14.5 g, 140 mmol), CuI (3.47 g, 18.22 mmol) and K2CO3 (31.56 g, 227.91 mmol) were mixed in DMF (200 mL), H2O (20 mL) and TEA (0.63 mL, 4.54 mmol). To the reaction mixture was then added 2-acetyl cyclohexanone (2.4 g, 17.1 mmol). The reaction mixture was stirred at 90° C. for 14 h. After completion of the reaction water was added. Aqueous layer was washed with ethyl acetate. Aqueous layer was made acidic by adding 1M citric acid solution (pH˜4). The product was extracted with ethyl acetate (3×200 mL). Combined organic layer was dried over anhydrous Na2SO4, and concentrated under reduced pressure to afford 16 g of 4-(2-carboxypropan-2-ylamino)-2-fluorobenzoic acid as crude product. This crude material was used as such for the next example.

後処理

  1. additionwas added
  2. washAqueous layer was washed with ethyl acetate
  3. additionby adding 1M citric acid solution (pH˜4)
  4. extractionThe product was extracted with ethyl acetate (3×200 mL)
  5. dry with materialCombined organic layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-6e39cf5449204359afe4963f9f3ab8fe
出典データセット
uspto-grants-2015_11
特許番号
US09174943B2

反応ノート

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