Reaktion #215772

Reaktionsgleichung

2-methoxy-4-(1-Boc-4-piperidyloxy)benzoyl chloride

ether

potassium hydroxide

N-Nitrosomethylurea

→

methyl 2-methoxy-4-(1-Boc-4-piperidyloxy)-phenylacetate

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwas cooled in ice
2. 2
   SonstigeThe ether layer was decanted
3. 3
   Trocknendried over solid potassium hydroxide for 15 min
4. 4
   SonstigeThe ether solution was decanted
5. 5
   Temperaturthe decanted solution was cooled in an ice bath
6. 6
   workup.WAITat ambient temperature for 3.5 hours
7. 7
   workup.WAITNitrogen was passed through the mixture for 1 hour
8. 8
   Einengenthe solution was then concentrated in vacuo
9. 9
   workup.DISSOLUTIONA portion (930 mg) of the residue was dissolved in methanol
10. 10
    Temperaturheated
11. 11
    Temperaturto reflux
12. 12
    workup.ADDITIONa solution of silver benzoate (200 mg) in triethylamine (2 ml) was added in five 0.1 ml portions at intervals of eight minutes
13. 13
    workup.ADDITIONA sixth portion was added after an additional forty minutes'
14. 14
    Temperaturreflux
15. 15
    workup.WAITafter another five minutes
16. 16
    TemperaturAfter a final 30 minutes' reflux
17. 17
    Temperaturthe mixture was cooled
18. 18
    Filtrationfiltered
19. 19
    Einengenthe filtrate was concentrated in vacuo
20. 20
    SonstigeThe residue was chromatographed on silica gel
21. 21
    Wascheneluted with 3%
22. 22
    Sonstigeevaporated to dryness in vacuo

Vorschrift

A mixture of ether (66 ml) and 40% aqueous potassium hydroxide (20 ml) was cooled in ice. N-Nitrosomethylurea (6.6 g) was added in portions with gentle swirling over 30 min. The ether layer was decanted and dried over solid potassium hydroxide for 15 min. The ether solution was decanted, and the decanted solution was cooled in an ice bath. A solution of 2-methoxy-4-(1-Boc-4-piperidyloxy)benzoyl chloride (3.26 g, 8.8 mmol) in THF (6 ml) was added dropwise and the mixture was stirred in the cold for 15 min and at ambient temperature for 3.5 hours. Nitrogen was passed through the mixture for 1 hour, and the solution was then concentrated in vacuo. A portion (930 mg) of the residue was dissolved in methanol and heated to reflux, and a solution of silver benzoate (200 mg) in triethylamine (2 ml) was added in five 0.1 ml portions at intervals of eight minutes. A sixth portion was added after an additional forty minutes' reflux, and after another five minutes, a seventh portion. After a final 30 minutes' reflux, the mixture was cooled and filtered, and the filtrate was concentrated in vacuo. The residue was chromatographed on silica gel eluted with 3%, followed by 5% methanol in methylene chloride. The product fractions were combined and evaporated to dryness in vacuo to give methyl 2-methoxy-4-(1-Boc-4-piperidyloxy)-phenylacetate.

Quelle