Water → Methyl 2-(isoquinolin-5-yl)acetate

HRID 353924

Reaktionsgleichung

Reaktionsgleichung von HRID 353924
[CH2:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][N:8]=[CH:9]2)[CH:2]=C.O.CO.C(O)[CH2:18][OH:19].[O-:21][Mn](=O)(=O)=O.[K+]>C(Cl)Cl.C(O)(=O)C>[CH3:18][O:19][C:2](=[O:21])[CH2:1][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][N:8]=[CH:9]2

Komponenten

7

Edukt 4

HCID 962WaterHCID 445171Poly(ethylene glycol) dimethyl ether (NHD)HCID 516875Potassium PermanganateHCID 220259635-Allylisoquinoline

Produkt 1

HCID 22337565Methyl 2-(isoquinolin-5-yl)acetate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

5-Allylisoquinoline (Preparation 6, Step 2; 169 mg, 1.0 mmol) in methylene chloride (2 mL), acetic acid (0.5 mL), and water (0.5 mL) was treated with dimethyl polyethylene glycol (Mn ca. 500, 95 uL, 100 mg, 0.2 mmol) in methylene chloride (1 mL) at 23° C. The mixture was cooled to 0° C. and powdered KMnO4 (521 mg, 3.3 mmol) was added portionwise, maintaining the temperature below 30° C. Following vigorous stirring for 18 h, the solvent was removed in vacuo and methanolic hydrogen chloride (10 mL, 1N) was added, and the mixture was refluxed for 4 h. The methanol was removed in vacuo, the residue was diluted with water, and the mixture was made basic with Na2CO3 (pH=9). The mixture was extracted with ethyl acetate, the resulting organic layer was washed with brine, was dried (MgSO4), was filtered, was concentrated in vacuo, and was purified by silica gel chromatography (2:1 hexanes—ethyl acetate) to afford isoquinolin-5-yl-acetic acid methyl ester; 1H NMR (400 MHz, CDCl3) δ9.28 (brs, 1H), 8.58 (d, J=6.2 Hz, 1H), 7.95 (d, J=7.9 Hz, 1H), 7.80 (d, J=5.8 Hz, 1H), 7.66 (d, J=5.8 Hz, 1H), 7.59 (t, J=7.6 Hz, 1H), 4.06 (s, 2H), 370 (s, 3H), MS (AP/Cl): 202.1 (M+H)+. Note: An impurity of 5-isoquinolylcarboxaldehyde was present following silica gel chromatography (ca. 20%).

Aufarbeitung

  1. temperaturemaintaining the temperature below 30° C
  2. customthe solvent was removed in vacuo and methanolic hydrogen chloride (10 mL, 1N)
  3. additionwas added
  4. temperaturethe mixture was refluxed for 4 h
  5. customThe methanol was removed in vacuo
  6. additionthe residue was diluted with water
  7. extractionThe mixture was extracted with ethyl acetate
  8. washthe resulting organic layer was washed with brine
  9. dry with materialwas dried (MgSO4)
  10. filtrationwas filtered
  11. concentrationwas concentrated in vacuo
  12. customwas purified by silica gel chromatography (2:1 hexanes—ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-20e3ab3fe4ff43f1b92b9e6ec4932e78
Quelldatensatz
uspto-grants-2004_06
Patentnummer
US06756385B2

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