Phosphorus oxide (P4O10) → 1-(3-Fluoro-4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline

HRID 445311ノート

反応式

HRID 445311 の反応式
[F:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[C:19]([F:22])([F:21])[F:20])[C:5]([NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=O.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.P(Cl)(Cl)(Cl)=O>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:5]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH2:9][CH2:8][N:7]=2)[CH:16]=[CH:17][C:18]=1[C:19]([F:22])([F:21])[F:20]

参加物

5

反応物 3

HCID 14812Phosphorus oxide (P4O10)HCID 24813Phosphorus oxychlorideHCID 595362643-Fluoro-N-phenethyl-4-(trifluoromethyl)benzamide

生成物 1

HCID 595364001-(3-Fluoro-4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline収率 74.1%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

To a stirred mixture of 3-fluoro-N-phenethyl-4-(trifluoromethyl)benzamide (1.27 g, 4.08 mmol) in 30 mL of toluene, phosphorus pentoxide (1.751 g, 12.3 mmol) and phosphorus oxychloride (1.90 mL, 20.4 mmol) were added. The mixture was refluxed for overnight. The reaction mixture was cooled to RT. Supernatant was removed and the ice-water was added to the flask containing the residue. The mixture was stirred to break the chunks into powder. EtOAc was added and the pH was adjusted to ˜12 with 3N aqueous potassium hydroxide. The layers were separated and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with water and saturated aqueous sodium chloride. The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo to afford 0.887 g of yellow viscous oil. The crude product was purified by silica gel chromatography (0-30% EtOAc in hexanes) to afford the title compound as a clear oil. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 7.63-7.73 (m, 1H) 7.39-7.54 (m, 3H) 7.31 (d, J=7.60 Hz, 2H) 7.16-7.24 (m, 1H) 3.84-3.96 (m, 2H) 2.77-2.89 (m, 2H).

後処理

  1. additionwere added
  2. temperatureThe mixture was refluxed for overnight
  3. customSupernatant was removed
  4. additionthe ice-water was added to the flask
  5. additioncontaining the residue
  6. additionEtOAc was added
  7. customThe layers were separated
  8. extractionthe aqueous phase was extracted with EtOAc
  9. washThe combined organic phases were washed with water and saturated aqueous sodium chloride
  10. dry with materialThe organic phase was dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-d7b322d3d5bf4e74837d8d16a509a8d1
出典データセット
uspto-grants-2013_07
特許番号
US08476297B2

反応ノート

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