Iodine → Trans-1,2,3,5,6,10b-hexahydro-6-(4'-iodophenyl)pyrrolo[2,1-a]isoquinoline

HRID 1275483

Reaktionsgleichung

Reaktionsgleichung von HRID 1275483
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([C@H:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C@H:16]3[CH2:23][CH2:24][CH2:25][N:15]3[CH2:14]2)=[CH:9][CH:8]=1.[I:26]I.CO>CCCCCC.C1COCC1.C(Cl)Cl.CCN(CC)CC>[I:26][C:7]1[CH:12]=[CH:11][C:10]([C@H:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C@H:16]3[CH2:23][CH2:24][CH2:25][N:15]3[CH2:14]2)=[CH:9][CH:8]=1

Komponenten

9

Edukt 4

HCID 807IodineHCID 887MethanolHCID 10830104trans-1,2,3,5,6,10b-Hexahydro-6-(4'-bromophenyl)pyrrolo[2,1-a]isoquinolineHCID 178418339Butyllithium

Produkt 1

HCID 20638627Trans-1,2,3,5,6,10b-hexahydro-6-(4'-iodophenyl)pyrrolo[2,1-a]isoquinolineAusbeute 50 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×HCID 8058HexaneLösungsmittelHCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a stirred solution of 1.6 M of butyllithium (0.63 mL, 1.0 mmol) in hexane was added slowly a solution of trans-1,2,3,5,6,10b-hexahydro-6-(4'-bromophenyl)pyrrolo[2,1-a]isoquinoline (100 mg, 0.3 mmol) in 5 mL of anhydrous THF at -78° C. under an argon atmosphere. After stirred at -78° C. for 5 min., a solution of iodine (252 mg, 1.0 mmol) in 5 mL of anhydrous. THF was added in one portion. The reaction mixture was stirred at -78° C. for 30 min and then at room temperature for further 15 min, quenched with ice-water (20 mL), extracted with methylene chloride (3×20 mL). The combined methylene chloride extract was washed with 10% sodium bisulfite solution, water, brine, dried over anhydrous MgSO4, filtered and concentrated to afford a yellow oil. Flash chromatography with 2.5% MeOH, 0.05% Et3N in methylene chloride gave 55 mg of thick colorless oil (50% yield). 1H NMR (CDCl3) δ 1.73-2.05 (m, 3H, C2H2 & C1H), 2.30-2.2.44 (m, 1H, C1H), 2.579 (dt, 1H, J=9.0, 8.7 Hz, C3H), 2.869 (dd, 1H, J=5.1, 11.1 Hz, C5H), 2.90-3.03 (m, 2H, C3H & C5H), 3.480 (dd, 1H, J=7.2, 9.0 Hz, C10bH), 4.125 (t, 1H, J=4.8 Hz, C6H), 6.865 (d, 1H, J=7.5 Hz, aryl), 6.995 (d, 2H, J=8.1 Hz, C6 phenyl aryl), 7.04-7.20 (m, 3H, aryl), 7.575 (d, 2H, J=8.1 Hz, C6 phenyl aryl); 13C NMR (CDCl3) δ 22.17 (C2), 30.31 (C1), 45.48 (C3), 54.13 (C10b), 55.95 (C6), 63.67 (C5), 91.60 (4'C), 125.73 (aromatic), 126.30, 129.30, 130.97, 137.23. HRMS calculated 375.0484 (for C18H18NI), measured 375.0490 (relative error 1.6 ppm).

Aufarbeitung

  1. stirringThe reaction mixture was stirred at -78° C. for 30 min
  2. waitat room temperature for further 15 min
  3. customquenched with ice-water (20 mL)
  4. extractionextracted with methylene chloride (3×20 mL)
  5. extractionThe combined methylene chloride extract
  6. washwas washed with 10% sodium bisulfite solution, water, brine
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford a yellow oil

Quellen und Nachweise

ORD-Eintrag
ord-a4225af2cdd74c2c9d3e235d6f62a5f6
Quelldatensatz
uspto-grants-2000_12
Patentnummer
US06162417

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