Reaktion #1247617

Reaktionsgleichung

MgCl2

ethyl magnesium malonate

4-methoxy-2-(methylthio)pyrimidine-5-carboxylic acid

oxalyl chloride

→

desired compound

Ausbeute 52.4%

Ethyl 3-(4-methoxy-2-(methylthio)pyrimidin-5-yl)-3-oxopropanoate

Ausbeute 52.4%

Lösungsmittel

THF

THF

H2O

EtOAc

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solvent was removed under reduced pressure
2. 2
   Sonstigethe crude acid chloride was used without purification in the next step
3. 3
   workup.STIRRINGstirred for additional 30 min
4. 4
   SonstigeThe layers were separated
5. 5
   Waschenthe organic layer was washed with brine (100 mL)
6. 6
   Trocknendried over Na2SO4
7. 7
   Einengenconcentrated
8. 8
   SonstigeThe crude was purified by flash chromatography (15% EtOAc/hexanes)

Vorschrift

A solution of 4-methoxy-2-(methylthio)pyrimidine-5-carboxylic acid (10.92 g, 54.6 mmol) and oxalyl chloride (19.0 mL, 217.8 mmol) in toluene (100 mL) was heated at 100° C. for 1 h. The solvent was removed under reduced pressure and the crude acid chloride was used without purification in the next step. To a solution of MgCl2 (7.80 g, 81.9 mmol) and ethyl magnesium malonate (14.10 g, 82.6 mmol) in THF (100 mL) was added the above acid chloride in THF (100 mL) at 0° C. followed by TEA (15.0 mL, 107.6 mmol). The reaction mixture was stirred at 0° C. for 30 min and at rt for 2 h. EtOAc (200 mL) and H2O (100 mL) were added and stirred for additional 30 min. The layers were separated and the organic layer was washed with brine (100 mL), dried over Na2SO4, and concentrated. The crude was purified by flash chromatography (15% EtOAc/hexanes) to yield the desired compound as a white solid (7.73 g, 52%). MS (m/z): 271 (MH+). 1H NMR (CDCl3) δ: 12.65 (s, 1H×⅔), 8.85 (s, 1H×⅓), 8.84 (s, 1H×⅔), 6.03 (s, 1H×⅔), 4.26 (q, 2H×⅔), 4.19 (q, 2H×⅓), 4.10 (s, 3H×⅔), 4.09 (s, 3H×⅓), 3.92 (s, 2H×⅓), 2.60 (s, 3H×⅓), 2.59 (s, 3H×⅔), 1.34 (t, 3H×⅔), 1.26 (3H×⅓).

Quelle