Methyl cyanoacetate → 2-Cyano-3-methyl-4-oxo-4-(2-trifluoromethyl-phenyl)-butyric acid methyl ester

HRID 383746ノート

反応式

HRID 383746 の反応式
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9](=[O:12])[CH2:10][CH3:11].BrBr.[H-].[Na+].[C:19]([CH2:21][C:22]([O:24][CH3:25])=[O:23])#[N:20].BrC(C)C(C1C=CC=CC=1C(F)(F)F)=O>C(Cl)(Cl)(Cl)Cl.C1COCC1>[CH3:25][O:24][C:22](=[O:23])[CH:21]([C:19]#[N:20])[CH:10]([CH3:11])[C:9](=[O:12])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[C:2]([F:1])([F:13])[F:14]

参加物

8

反応物 5

HCID 7747Methyl cyanoacetateHCID 24408BromineHCID 24758Sodium hydrideHCID 1400402-(Trifluoromethyl)propiophenoneHCID 201874742-Bromo-1-[2-(trifluoromethyl)phenyl]propan-1-one

生成物 1

HCID 598075352-Cyano-3-methyl-4-oxo-4-(2-trifluoromethyl-phenyl)-butyric acid methyl ester収率 93%

試薬・触媒・溶媒 2

HCID 5943Carbon Tetrachloride溶媒2 回HCID 8028Tetrahydrofuran溶媒

反応条件

温度
20 °C

実験手順

To a solution of 2′-trifluoromethyl-propiophenone (10 g, 48 mmol) in carbon tetrachloride (50 ml) was added a solution of bromine (2.72 mL, 52.8 mmol) in carbon tetrachloride (20 mL) dropwise. After the addition was complete, stirring was continued for another 2 h. The solution was washed with satd NaHCO3 and water, dried (anhyd Na2SO4) and concentrated under reduced pressure to give 2-bromo-1-(2-trifluoromethyl-phenyl)-propan-1-one as an oil (12.8 g, 95%), which was used in the next step without purification. 1H-NMR (CDCl3): δ 7.73 (m, 2H), 7.58-7.67 (m, 2H), 4.96 (q, 1H), 1.90 (d, 3H). To a solution of 2′-trifluoromethyl-propiophenone (10 g, 48 mmol) in carbon tetrachloride (50 ml) was added a solution of bromine (2.72 mL, 52.8 mmol) in carbon tetrachloride (20 m To a suspension of NaH (60%, 2.88 g, 72 mmol) in anhyd THF (200 mL) was added methyl cyanoacetate (4.5 mL, 50 mmol). After this mixture was stirred for 3 h at 20° C., a solution of 2-bromo-1-(2-trifluoromethyl-phenyl)-propan-1-one (13.5 g, 48 mmol) was added and the mixture was stirred overnight at 20° C. The mixture was quenched with water and the organic layer was separated. The aqueous layer was extracted with EtOAc. The combined extracts were washed with brine, dried (anhyd Na2SO4) and concentrated under reduced pressure to afford the title compound as an oil (13.3 g, 93%), which was used in the next step without purification. MS (ES): 300 (MH+).

後処理

  1. customwas used in the next step without purification
  2. stirringthe mixture was stirred overnight at 20° C
  3. customThe mixture was quenched with water
  4. customthe organic layer was separated
  5. extractionThe aqueous layer was extracted with EtOAc
  6. washThe combined extracts were washed with brine
  7. dry with materialdried (anhyd Na2SO4)
  8. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-a3ee0a4724ff4f4e9d1a18afdf108462
出典データセット
uspto-grants-2013_02
特許番号
US08367667B2

反応ノート

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