Reaktion #1955834

Reaktionsgleichung

MgCl2

diethyl malonate

4-(3-bromo-4-methoxyphenyl)-tetrahydro-2H-pyran-4-carboxylic acid

thionyl chloride

→

intermediate

Ausbeute 16.1%

Diethyl 2-(4-(3-bromo-4-methoxyphenyl)-tetrahydro-2H-pyran-4-carbonyl)malonate

Ausbeute 16.1%

Lösungsmittel

ACN

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe resulting mixture was then stirred at room temperature for 2.5 hours
2. 2
   Temperaturwas refluxed for 2 hours
3. 3
   Einengenconcentrated in vacuo
4. 4
   workup.ADDITIONThe residue was diluted with 10 mL ACN
5. 5
   workup.ADDITIONadded dropwise to the above mixture
6. 6
   workup.STIRRINGThe mixture was stirred at 50° C. for 15 hours
7. 7
   TemperaturThe mixture was cooled to room temperature
8. 8
   workup.ADDITIONdiluted with 100 mL ether
9. 9
   Waschenwashed with H2O (2×50 mL) and brine (20 mL)
10. 10
    Trocknendried over anhydrous Na2SO4
11. 11
    Einengenconcentrated in vacuo
12. 12
    SonstigeThe crude product was purified by column chromatography
13. 13
    Wascheneluting with 10-20% EtOAc/hexane

Vorschrift

A mixture of diethyl malonate (2.8 g, 17 mmol) in 50 mL ACN was stirred at 0° C. This mixture was treated with MgCl2 (1.7 g, 17 mmol) in one portion and dropwise with TEA (3.9 g, 38 mmol). The resulting mixture was then stirred at room temperature for 2.5 hours. A mixture of 4-(3-bromo-4-methoxyphenyl)-tetrahydro-2H-pyran-4-carboxylic acid (5.5 g, 17 mmol) in thionyl chloride (21 g, 175 mmol) was refluxed for 2 hours and then concentrated in vacuo. The residue was diluted with 10 mL ACN and added dropwise to the above mixture. The mixture was stirred at 50° C. for 15 hours, M−1=455/457. The mixture was cooled to room temperature, diluted with 100 mL ether, washed with H2O (2×50 mL) and brine (20 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The crude product was purified by column chromatography eluting with 10-20% EtOAc/hexane to give 1.25 g of the intermediate as a pale yellow oil. MS m/e=455/457 (M+H)+.

Quelle