Reaktion #322323

Reaktionsgleichung

1-methyl-4-piperidone

8-bromo-2-(dibenzylamino)-naphthalene

hexane

butyllithium

→

7-dibenzylamino-1-(4-hydroxy-1-methyl-4-piperidinyl)-naphthalene

Ausbeute 138.8%

Lösungsmittel

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe following reaction
2. 2
   Sonstigepurification
3. 3
   workup.ADDITIONwas added dropwise
4. 4
   Waschenrinse
5. 5
   workup.STIRRINGwhile stirring
6. 6
   workup.WAITwas continued 20 minutes at -100° C
7. 7
   Sonstigequenched with water
8. 8
   SonstigeThe solvent was removed
9. 9
   Sonstigethe residue was partitioned between methylene chloride and water (at this point the two reactions
10. 10
    SonstigeThe phases were separated
11. 11
    Waschenthe organic layer was washed with brine
12. 12
    Sonstigedried
13. 13
    Einengenconcentrated onto silica gel
14. 14
    EinengenThe combined eluents were concentrated
15. 15
    workup.DISSOLUTIONredissolved in methylene chloride
16. 16
    SonstigeThe solution was dried
17. 17
    Einengenconcentrated

Vorschrift

The following reaction was run in two side by side reactions and the crude products were combined for work up and purification. A mechanically stirred solution of 8-bromo-2-(dibenzylamino)-naphthalene (10.0 g, 24.9 mmol from Preparation 4) in tetrahydrofuran (200 mL) was cooled to -95° C. (hexane/liquid nitrogen) and butyllithium (10.39 mL, 24.9 mmol, 2.4 M) was added dropwise. The orange solution was stirred 7 min, then 1-methyl-4-piperidone (2.82 g, 24.9 mmol) was added dropwise over 10 minutes with a 10 mL tetrahydrofuran rinse. The orange color faded while stirring was continued 20 minutes at -100° C. The reaction was allowed to warm to room temperature and quenched with water. The solvent was removed and the residue was partitioned between methylene chloride and water (at this point the two reactions were combined). The phases were separated and the organic layer was washed with brine, dried, and concentrated onto silica gel. Flash chromatography (4×4 inches silica gel) proceeded as follows: methylene chloride (1 L) and 2% methanol/methylene chloride (1.6 L) unweighed white solid 7-dibenzylaminonaphthalene; 15% methanol / methylene chloride (1 L), 25% methanol/methylene chloride (1 L) and 30% methanol/methylene chloride/0.2% ammonium hydroxide (4 L) product contaminated with water. The combined eluents were concentrated and redissolved in methylene chloride. The solution was dried and concentrated to afford 15.09 g (69%) of 7-dibenzylamino-1-(4-hydroxy-1-methyl-4-piperidinyl)-naphthalene as a light tan foam. A sample recrystallized from ethyl acetate had mp 173°-174° C. Analysis calculated for C30H32N2O: C, 82.53; H, 7.39; N, 6.42. Found: C, 82.42; H, 7.44; N, 6.38.

Quelle