Reaktion #544917

Reaktionsgleichung

lithium diisopropylamide

diethyl isopropylidenemalonate

hydrochloric acid

α-[3-(dimethylamino)propyl]-3-methoxybenzeneacetonitrile

→

white powder

diethyl 2-[2-cyano-5-(dimethylamino)-2-(3-methoxy-phenyl)-1,1-dimethylpentyl]propanedioate, monohydrochloride

Lösungsmittel

tetrahydrofuranne heptane

tetrahydrofuran

water

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeA nitrogen atmosphere was applied to a reaction vessel
2. 2
   TemperaturThe solvent was cooled to less than −40° C.
3. 3
   Sonstigedid not exceed −50° C
4. 4
   Sonstigethe cold reaction mixture
5. 5
   Temperaturcooled to 10° C
6. 6
   ExtraktionThe mixture was extracted twice with toluene
7. 7
   Extraktionthe toluene phase is back extracted with a solution of 2 ml of hydrochloric acid (36% w/w) in 8 ml of water
8. 8
   ExtraktionThe aqueous acidic extract
9. 9
   Extraktionextracted twice with 50 ml portions of methylene chloride
10. 10
    WaschenThe combined methylene chloride extracts were washed with water
11. 11
    Filtrationthe methylene chloride phase filtered
12. 12
    Einengenconcentrated to low volume by distillation at atmospheric pressure
13. 13
    workup.ADDITIONA 100 ml portion of ethyl acetate was added
14. 14
    Temperaturthe resulting slurry cooled to 5–10° C
15. 15
    FiltrationThe resulting solid was collected by filtration
16. 16
    Waschenwashed with ethyl acetate
17. 17
    Sonstigedried at 50° C.

Vorschrift

A nitrogen atmosphere was applied to a reaction vessel and 50 ml of dry tetrahydrofuran is added. The solvent was cooled to less than −40° C. and 32 mmoles of lithium diisopropylamide in tetrahydrofuranne-heptane was added (16 ml of a 2 M solution). A solution of 6.97 g (30 mmoles) of α-[3-(dimethylamino)propyl]-3-methoxybenzeneacetonitrile in 30 ml of tetrahydrofuran was added at less than −20° C. and left at this temperature for 30 min. The mixture was then cooled to −50° C. and a solution of 6.62 g (33 mmoles) of diethyl isopropylidenemalonate in 30 ml of tetrahydrofuran was added to the reaction mixture at a rate such that the temperature did not exceed −50° C. The mixture was stirred at −50° C. for 30 min and the cold reaction mixture added to a stirred solution of 30 ml of aqueous hydrochloric acid (36% w/w) in 100 ml of water cooled to 10° C. The mixture was extracted twice with toluene and the toluene phase is back extracted with a solution of 2 ml of hydrochloric acid (36% w/w) in 8 ml of water. The aqueous acidic extract was combined with the aqueous acidic phase from above and extracted twice with 50 ml portions of methylene chloride. The combined methylene chloride extracts were washed with water and the methylene chloride phase filtered and concentrated to low volume by distillation at atmospheric pressure. A 100 ml portion of ethyl acetate was added and the resulting slurry cooled to 5–10° C. The resulting solid was collected by filtration, washed with ethyl acetate and dried at 50° C. to give 10.1 g of white powder.

Quelle