Reaktion #1335682

Reaktionsgleichung

Water

1-methyl-4-piperidone

2-bromofluorobenzene

n-butyllithium

→

4-(2-fluorophenyl)-4-hydroxy-1-methylpiperidine

Lösungsmittel

tetrahydrofuran

tetrahydrofuran

—

ethyl acetate ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONAfter total addition
2. 2
   Sonstigeresults in a tan colored solution
3. 3
   workup.ADDITIONis added to the solution at a rate
4. 4
   Temperaturto maintain the reaction medium's temperature below -60° C
5. 5
   workup.ADDITIONAfter total addition
6. 6
   workup.STIRRINGthe reaction mixture is stirred at the same low temperature for one hour
7. 7
   Sonstigeto separate into its organic
8. 8
   SonstigeThe organic phase is collected
9. 9
   Extraktionthe aqueous phase is extracted thrice with ether
10. 10
    ExtraktionThe combined organic solution is extracted with an excess of 2N hydrochloric acid
11. 11
    Sonstigeproducing a heavy oil which
12. 12
    SonstigeThis solution is dried
13. 13
    Einengenconcentrated to dryness
14. 14
    Sonstigeleaving a viscous oil which
15. 15
    Sonstigecrystallizes
16. 16
    Temperaturwith cooling
17. 17
    SonstigeThe solid product is recrystallized from a benzene-hexane mixture

Vorschrift

46 ml of 2.4M n-butyllithium are added over a 15 minute span to a mixture cooled to -70° C. of 17.5 g of 2-bromofluorobenzene and 50 ml of tetrahydrofuran. After total addition, the reaction mixture is stirred at between -60° to -70° C. for 15 minutes to enable complete lithiation, which results in a tan colored solution. A mixture of 11.3 g of 1-methyl-4-piperidone in 20 ml of tetrahydrofuran is added to the solution at a rate to maintain the reaction medium's temperature below -60° C. After total addition, the reaction mixture is stirred at the same low temperature for one hour before being permitted to warm to ambient temperature. Water is added and the biphasic mixture is permitted to separate into its organic and aqueous phases. The organic phase is collected and the aqueous phase is extracted thrice with ether and the ether extracts are combined with the organic phase. The combined organic solution is extracted with an excess of 2N hydrochloric acid and then discarded. The acidic solution is basified with ammonium hydroxide, producing a heavy oil which is dissolved in a 1:1 ethyl acetate ether mixture. This solution is dried and then concentrated to dryness, leaving a viscous oil which crystallizes with cooling. The solid product is recrystallized from a benzene-hexane mixture to give prisms, mp 127°-129° C. of 4-(2-fluorophenyl)-4-hydroxy-1-methylpiperidine.

Quelle