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

HRID 2070761노트

반응식

HRID 2070761 반응식
[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]

참가 물질

6

반응물 4

HCID 962WaterHCID 11534Bromoacetonitrile2회HCID 81531Diisopropylethylamine2회HCID 47002571Methyl 3-amino-5-fluoro-4-methylbenzoate

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-242bcfe52e9f437184497dd2d5313e27
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08299246B2

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