Water → Methyl 3-(cyanomethylamino)-5-fluoro-4-methylbenzoate

HRID 1697344ノート

反応式

HRID 1697344 の反応式
[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([F:10])[C:7]([CH3:11])=[C:6]([NH2:12])[CH:5]=1.[CH:14]([N:17](CC)C(C)C)(C)[CH3:15].BrCC#N.O>C1COCC1>[C:14]([CH2:15][NH:12][C:6]1[CH:5]=[C:4]([CH:9]=[C:8]([F:10])[C:7]=1[CH3:11])[C:3]([O:2][CH3:1])=[O:13])#[N:17]

参加物

6

反応物 4

HCID 962WaterHCID 11534Bromoacetonitrile2 回HCID 81531Diisopropylethylamine2 回HCID 47002571Methyl 3-amino-5-fluoro-4-methylbenzoate

生成物 1

HCID 86661587Methyl 3-(cyanomethylamino)-5-fluoro-4-methylbenzoate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a stirred solution of 3-amino-5-fluoro-4-methyl-benzoic acid methyl ester (Example 252e, 34.7 g) in THF (300 mL) at room temperature was added N,N-diisopropylethylamine (61.2 mL) followed by bromoacetonitrile (24.41 mL). The mixture was heated at reflux for 16 h, further bromoacetonitrile (4.8 mL) and N,N-diisopropylethylamine (12.5 mL) were added and heating was continued for 6 h. The reaction was cooled to room temperature and concentrated. 1N HCl (600 mL) and dichloromethane (800 mL) were added. This gave some solid precipitate which did not dissolve. Water (300 mL) was added to help identify layers. The lower organic layer containing solid and a bit of water was separated and this organic fraction was washed with 1M HCl/brine (400 mL of 1:1 mixture) before being dried (MgSO4). A second drying (Na2SO4) was needed. After the drying agent was filtered off (washed through with 400 ml dichloromethane) the filtrate was concentrated (˜60 g). This was azeotroped with toluene (400 mL) and final solvent removal gave subtitle compound (39.4 g).

後処理

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 16 h
  3. temperatureheating
  4. concentrationconcentrated
  5. addition1N HCl (600 mL) and dichloromethane (800 mL) were added
  6. customThis gave some solid precipitate which
  7. dissolutiondid not dissolve
  8. additionThe lower organic layer containing solid
  9. customa bit of water was separated
  10. washthis organic fraction was washed with 1M HCl/brine (400 mL of 1:1 mixture)
  11. dry with materialbefore being dried (MgSO4)
  12. dry with materialA second drying (Na2SO4)
  13. filtrationAfter the drying agent was filtered off
  14. wash(washed through with 400 ml dichloromethane) the filtrate
  15. concentrationwas concentrated (˜60 g)
  16. customThis was azeotroped with toluene (400 mL) and final solvent removal

出典と根拠

ORDレコード
ord-679b9eb926a0408499b74ba173f15a8b
出典データセット
uspto-grants-2012_04
特許番号
US08163905B2

反応ノート

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