2-Aminophenol → 5-(1,3-Benzoxazol-2-yl)-2-methoxy benzonitrile

HRID 7758

反応式

HRID 7758 の反応式
[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:6]([OH:8])=O)#[N:2].O=S(Cl)Cl.[NH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1O.C(N(CC)CC)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>CCOC(C)=O.C1COCC1>[O:8]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[N:18]=[C:6]1[C:5]1[CH:9]=[CH:10][C:11]([O:12][CH3:13])=[C:3]([CH:4]=1)[C:1]#[N:2]

参加物

8

反応物 5

HCID 58012-AminophenolHCID 6101p-Toluenesulfonic acidHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 219909723-Cyano-4-methoxybenzoic acid

生成物 1

HCID 219909835-(1,3-Benzoxazol-2-yl)-2-methoxy benzonitrile

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of methyl 3-cyano-4-methoxy-benzoate (1.5 g, 7.9 mmol) in CH3OH/H2O (25 mL; 1:1), was added LiOH (2.5 g, 60.0 mmol). The reaction mixture was refluxed for 2 h, cooled at rt and 6M HCl was added dropwise until pH 2 was obtained. The precipitate was collected, washed with H2O (3×20 mL), dried in vacuo to afford 3-cyano-4-methoxy-benzoic acid. MS (ESI) 178 (M+H)+. To a 100 mL round-bottom flask with 3-cyano-4-methoxy-benzoic acid (1.4 g, 7.8 mmol), was added SOCl2 (15 mL) dropwise. The reaction was refluxed for 1 h and was cooled to rt. The excess of SOCl2 was removed in vacuo and the oily acid chloride was dissolved in THF (15 mL). The resulting solution was added dropwise to a mixture of 2-aminophenol (1.3 g, 11.7 mmol), triethylamine (1.3 g, 11.7 mmol) and THF (30 mL) at 0° C. The reaction was warmed up to rt and stirred an additional 3 h. The precipitate was removed by filtration and the filtrate was concentrated and dried in vacuo. The dark brown solid residue was dissolved in toluene (20 mL) and p-toluenesulfonic acid (6.0 g, 46.8 mmol) was added. The reaction was refluxed overnight, cooled to rt, and EtOAc (300 mL) was added. The EtOAc solution was washed with brine (3×20 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, CHCl3:CH3OH 8:1) to afford 5-(1,3-benzoxazol-2-yl)-2-methoxy benzonitrile. MS ESI) 251(M+H)+.

後処理

  1. temperatureThe reaction was refluxed for 1 h
  2. customThe excess of SOCl2 was removed in vacuo
  3. dissolutionthe oily acid chloride was dissolved in THF (15 mL)
  4. temperatureThe reaction was warmed up to rt
  5. customThe precipitate was removed by filtration
  6. concentrationthe filtrate was concentrated
  7. customdried in vacuo
  8. dissolutionThe dark brown solid residue was dissolved in toluene (20 mL)
  9. temperatureThe reaction was refluxed overnight
  10. temperaturecooled to rt
  11. washThe EtOAc solution was washed with brine (3×20 mL)
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe residue was purified by flash chromatography (silica gel, CHCl3:CH3OH 8:1)

出典と根拠

ORDレコード
ord-43b89c92a2b543e48b4da1a4e02abf86
出典データセット
uspto-grants-2006_08
特許番号
US07087601B2

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