Reaction #65197

Reaction equation

methyl acetoacetate

sodium hydride

tetrahydrofuran

compound

(E)-3-[4-(4-Fluorophenyl)-6-isopropyl-2-methoxy-3-methoxymethyl-pyridin-5-yl]-prop-2-enal

tetrahydrofuran

butyllithium

→

Methyl (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-methoxy-3-methoxy-methyl-pyridin-5-yl]-5-hydroxy-3-oxo-hept-6-enoate

Solvents

ammonium chloride

n-hexane

ether

Conditions

Workup

1. 1
   workup.ADDITIONare then added dropwise
2. 2
   workup.STIRRINGthe mixture is stirred at -5° C. for 30 min
3. 3
   Extractionthe mixture is extracted three times with 100 ml of ether each time
4. 4
   WashThe combined organic phases are washed twice with saturated sodium hydrogen carbonate solution and once with saturated sodium chloride solution
5. 5
   Dryingdried over sodium sulphate
6. 6
   Concentrationconcentrated in vacuo

Procedure

0.35 ml (3.3 mmol) of methyl acetoacetate are added dropwise under nitrogen to a suspension of 80 mg (3.4 mmol) of sodium hydride in 3 ml of dry tetrahydrofuran at -5° C. After 15 min, 2.3 ml (3.3 mmol) of 15% strength butyllithium in n-hexane and 3.3 ml (3.3 mmol) of a 1 molar zinc chloride solution in ether are added dropwise at the same temperature and the mixture is stirred for 15 min. 530 mg (1.5 mmol) of the compound from Example 10 dissolved in 8 ml of dry tetrahydrofuran are then added dropwise and the mixture is stirred at -5° C. for 30 min. The reaction solution is cautiously diluted with 100 ml of saturated aqueous ammonium chloride solution and the mixture is extracted three times with 100 ml of ether each time. The combined organic phases are washed twice with saturated sodium hydrogen carbonate solution and once with saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo.

Source