Reaktion #346168

Reaktionsgleichung

4-[4-(1-adamantyl)-2-amino-phenoxy]-butyric acid methyl ester

hydrochloric acid

sodium nitrite

→

4-[4-(1-adamantyl)-2-chlorophenoxy]-butyric acid

Lösungsmittel

water

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONAfter completion of the addition
2. 2
   FiltrationThe reaction solution is then filtered cold
3. 3
   Sonstigekept at 0° C
4. 4
   workup.ADDITIONis then added in portions to a solution of 5 g of freshly prepared copper-(I) chloride in 20 ml of concentrated hydrochloric acid at 0° C
5. 5
   workup.STIRRINGwhilst stirring
6. 6
   workup.ADDITIONAfter completion of the addition
7. 7
   Sonstigeto rise to about 25° C
8. 8
   Temperaturthe mixture is then heated on a water bath until the evolution of nitrogen
9. 9
   FiltrationIt is then filtered
10. 10
    Waschenthe residue is well rinsed with methylene chloride
11. 11
    Sonstigethe filtrate is partitioned between 3 times 50 ml of methylene chloride and 50 ml of water
12. 12
    Sonstigeevaporated in vacuo
13. 13
    workup.DISSOLUTIONThe evaporation residue is dissolved in 100 ml of ethanol
14. 14
    workup.WAIT20 ml of 2 N sodium hydroxide solution and the mixture is left
15. 15
    workup.WAITto stand for 24 hours at about 25° C
16. 16
    SonstigeIt is then evaporated to dryness in vacuo
17. 17
    Sonstigethe evaporation residue is partitioned between 150 ml of 2 N hydrochloric acid and twice 50 ml of methylene chloride
18. 18
    WaschenThe organic phases are washed until neutral,
19. 19
    Trocknendried over sodium sulphate
20. 20
    Sonstigeevaporated in vacuo
21. 21
    SonstigeChromatography of the evaporation residue on 100 g of silica gel, with ether as the migrating agent, and subsequent crystallisation from ethanol

Vorschrift

1.00 g of sodium nitrite in 5 ml of water is added dropwise, whilst stirring, to a suspension of 5 g of 4-[4-(1-adamantyl)-2-amino-phenoxy]-butyric acid methyl ester in 10 ml of concentrated hydrochloric acid and 30 ml of water. After completion of the addition, the mixture is stirred for a further 3 hours at 0° C. The reaction solution is then filtered cold. The filtrate, kept at 0° C, is then added in portions to a solution of 5 g of freshly prepared copper-(I) chloride in 20 ml of concentrated hydrochloric acid at 0° C, whilst stirring. After completion of the addition, the temperature is allowed to rise to about 25° C and the mixture is then heated on a water bath until the evolution of nitrogen has ceased. It is then filtered, the residue is well rinsed with methylene chloride, and the filtrate is partitioned between 3 times 50 ml of methylene chloride and 50 ml of water. The organic phases are combined and evaporated in vacuo. The evaporation residue is dissolved in 100 ml of ethanol and 20 ml of 2 N sodium hydroxide solution and the mixture is left to stand for 24 hours at about 25° C. It is then evaporated to dryness in vacuo and the evaporation residue is partitioned between 150 ml of 2 N hydrochloric acid and twice 50 ml of methylene chloride. The organic phases are washed until neutral, dried over sodium sulphate and evaporated in vacuo. Chromatography of the evaporation residue on 100 g of silica gel, with ether as the migrating agent, and subsequent crystallisation from ethanol, gives 4-[4-(1-adamantyl)-2-chlorophenoxy]-butyric acid of melting point 164°-166° C.

Quelle