Hydrochloric Acid → 5-cyano-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid

HRID 513200노트

반응식

HRID 513200 반응식
C(C1C=C2C(=CC=1)NC(C(OCC)=O)=C2)#N.FC(F)(F)OC1C=CC(OCCO)=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[C:65]([C:67]1[CH:68]=[C:69]2[C:73](=[CH:74][CH:75]=1)[N:72]([CH2:76][CH2:77][O:78][C:79]1[CH:84]=[CH:83][C:82]([O:85][C:86]([F:89])([F:88])[F:87])=[CH:81][CH:80]=1)[C:71]([C:90]([O:92]CC)=[O:91])=[CH:70]2)#[N:66].[OH-].[Na+].Cl>C1(C)C=CC=CC=1.CCOC(C)=O.C1COCC1.O.CO>[C:65]([C:67]1[CH:68]=[C:69]2[C:73](=[CH:74][CH:75]=1)[N:72]([CH2:76][CH2:77][O:78][C:79]1[CH:80]=[CH:81][C:82]([O:85][C:86]([F:87])([F:88])[F:89])=[CH:83][CH:84]=1)[C:71]([C:90]([OH:92])=[O:91])=[CH:70]2)#[N:66]

참가 물질

13

반응물 7

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 4714953Ethyl 5-cyanoindole-2-carboxylateHCID 5363146Diisopropyl azodicarboxylateHCID 211086172-[4-(Trifluoromethoxy)phenoxy]ethanolHCID 71212567ethyl 5-cyano-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylate

생성물 1

HCID 712121305-cyano-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid수율 85.8%

시약·촉매·용매 5

HCID 887Methanol용매HCID 962Water용매HCID 1140Toluene용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution Ethyl 5-cyano-1H-indole-2-carboxylate (37 mg, 0.173 mmol), 2-[4-(trifluoromethoxy) phenoxy]ethanol (42 mg, 0.19 mmol) and Triphenylphosphine (227 mg, 0.518 mmol) in toluene (1 mL) was add DIAD (0.044 ml, 0.225 mmol) dropwise at RT. The reaction was let to stir overnight. The mixture was diluted with EtOAc and quenched with water. The two layers were separated, and the aqueous phase was further extracted twice with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by normal phase silica chromatography. The eluting solvent was 0-30% EtOAc in Hexanes. The isolated ethyl 5-cyano-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylate (15 mg, 0.04 mmol) was dissolved in THF (1 mL), MeOH (300 uL) and 1M NaOH (200 uL). The reaction went to completion in 5 hr. Water was added, the pH was adjusted to 3 with 1N HCl, and the solvent was removed in vacuo. EtOAc was added to the resulting aqueous solution. The two layers were separated, and the aqueous phase was further extracted twice with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to yield 13.4 mg of the title product. HRMS: Calc for C19H13F3N2O4 413.0720. Found 413.0718

후처리

  1. customquenched with water
  2. customThe two layers were separated
  3. extractionthe aqueous phase was further extracted twice with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by normal phase silica chromatography
  9. waitThe reaction went to completion in 5 hr
  10. customthe solvent was removed in vacuo
  11. additionEtOAc was added to the resulting aqueous solution
  12. customThe two layers were separated
  13. extractionthe aqueous phase was further extracted twice with EtOAc
  14. washThe combined organic layers were washed with brine
  15. dry with materialdried (Na2SO4)
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-715a5af52da54067a6b3f7b777a2190d
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09102673B2

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