Reaktion #160396

Reaktionsgleichung

HCl

K2CO3

18-crown-6

N-(4-Methoxy-benzyl)-N-(2-methoxycarbonyl-ethyl)-malonamic acid methyl ester

→

1-(4-Methoxy-benzyl)-piperidine-2,4-dione

Ausbeute 69.0%

Lösungsmittel

toluene

water

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturunder nitrogen, was heated
2. 2
   Temperaturto reflux
3. 3
   workup.ADDITIONtreated
4. 4
   TemperaturAfter 7 h at reflux the reaction
5. 5
   Temperaturcooled to 0°
6. 6
   ExtraktionThe mixture was then extracted several times with CH2Cl2 (3×80 ml)
7. 7
   Sonstigethe combined organics dried
8. 8
   Sonstigeevaporated to a brown oil (1.33 g)
9. 9
   workup.ADDITIONThe brown oil was treated with 10% aqueous oxalic acid
10. 10
    Temperaturheated
11. 11
    Temperaturto reflux for 6.5 h
12. 12
    ExtraktionThe mixture was then extracted repratedly with CH2Cl2
13. 13
    Sonstigethe combined organics dried
14. 14
    Sonstigeevaporated to a dirty yellow oil (1.03 g)
15. 15
    SonstigeThe crude material was purified on silica gel using (CH2Cl2:MeOH=30:1) as eluent

Vorschrift

A mixture of anhydrous K2CO3 (3.2 g, 23.2 mmol, 5 eq) and 18-crown-6 (azetroped several times with toluene) (122 mg, 0.464 mmol, 10 mol %) in dry toluene (4 ml), under nitrogen, was heated to reflux and then treated, dropwise, over 40 min, with a solution of N-(4-Methoxy-benzyl)-N-(2-methoxycarbonyl-ethyl)-malonamic acid methyl ester. After 7 h at reflux the reaction was diluted with water (4 ml) and toluene (4 ml), then cooled to 0° and carefully acudified to pH 1.7 with 0.1N HCl. The mixture was then extracted several times with CH2Cl2 (3×80 ml) and the combined organics dried and evaporated to a brown oil (1.33 g). The brown oil was treated with 10% aqueous oxalic acid and heated to reflux for 6.5 h. The mixture was then extracted repratedly with CH2Cl2 and the combined organics dried and evaporated to a dirty yellow oil (1.03 g). The crude material was purified on silica gel using (CH2Cl2:MeOH=30:1) as eluent to give 1-(4-Methoxy-benzyl)-piperidine-2,4-dione as a pale brown solid (750 mg, 69%); (300 MHz, CDCl3) 2.52 (t, J=5.7 HZ, 2H), 3.41 (s, 2H), 3.47 (t, J=5.7 Hz, 2H), 3.80 (s, 3H), 4.62 (s, 2H), 6.16-6.88 (m, 2H), 7.20 (m, 2H).

Quelle