Hydrogen chloride-ethyl acetate → 8-Chloro-3-(4-methoxy-benzyl)-8-(3-methoxy-phenyl)-3-aza-bicyclo[3.2.1]octane

HRID 1295500Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1295500
[CH3:1][O:2][C:3]1[CH:26]=[CH:25][C:6]([CH2:7][N:8]2[CH2:14][CH:13]3[C:15]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=4)(O)[CH:10]([CH2:11][CH2:12]3)[CH2:9]2)=[CH:5][CH:4]=1.[ClH:27].CCOC(C)=O>CCOC(C)=O>[Cl:27][C:15]1([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=2)[CH:13]2[CH2:12][CH2:11][CH:10]1[CH2:9][N:8]([CH2:7][C:6]1[CH:25]=[CH:26][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[CH2:14]2

Komponenten

4

Edukt 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 694310753-(4-Methoxy-benzyl)-8-(3-methoxy-phenyl)-3-aza-bicyclo[3.2.1]octan-8-ol

Produkt 1

HCID 694314818-Chloro-3-(4-methoxy-benzyl)-8-(3-methoxy-phenyl)-3-aza-bicyclo[3.2.1]octane

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

3-(4-Methoxy-benzyl)-8-(3-methoxy-phenyl)-3-aza-bicyclo[3.2.1]octan-8-ol (1.48 g, 4.19 mmol) was dissolved in EtOAc (20 mL), charged with 2.5N HCl/EtOAc (6 mL), and azeotroped with MeOH (2×50 mL) to yield the HCl salt. This salt was slurried in CH2Cl2 (20 mL) and pyridine (0.34 mL, 4.19 mmol) then treated with thionyl chloride (0.92 mL, 12.6 mmol) dropwise, causing the dispersion to dissolve. The reaction was judged complete by TLC after 2 h, at which time it was carefully added to 1N NaOH (50 mL) at 0° C., bringing the final pH to 9. The product was extracted with CH2Cl2 (3×20 mL), washed with saturated aqueous NaCl solution (1×50 mL), filtered through a cotton plug and concentrated to brown oil. Flash chromatography provided a white solid (1.31 g, 84%). (TLC 40% EtOAc/hexanes Rf 0.75); 1H NMR (400 MHz, CDCl3) δ 7.23 (m, 3H), 7.04 (d, J=7.5 Hz, 1H), 6.99 (s, 1H), 6.84 (d, J=8.7 Hz, 2H), 6.79 (dd, J=7.9, 2.1 Hz, 1H), 3.78 (s, 6H), 3.53 (br s, 2H), 2.95 (d, J=10.3 Hz, 2H), 2.67 (br s, 2H), 2.65 (m, 2H), 1.79 (d, J=1.0 Hz, 2H), 1.45 (m, 2H); LCMS m/z 372.2 (M+1)+; mp 99–102° C.

Aufarbeitung

  1. customazeotroped with MeOH (2×50 mL)

Quellen und Nachweise

ORD-Eintrag
ord-94abec4de4ac4af2bca99025d039732c
Quelldatensatz
uspto-grants-2007_07
Patentnummer
US07241887B2

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