Sodium hydride → 6-(2-Methyl-1-oxo-1,2,3,4-tetrahydro-naphthalen-2-yl)-hexanoic acid

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Reaction Steps

To a suspension of 0.7 g NaH in 40 mL of dry THF are added 4.0 g 2-methyl-1-tetralon in 20 mL of THF. After stirring for 30 min, 5.5 g ethyl-6-bromo-hexanoate in 10 mL of THF are added and the mixture is refluxed for 6 h. After evaporation of the solvent the residue is dissolved in a solution of 4.16 g potassium hydroxide in 50 mL of MeOH and 20 mL of H2O and heated to reflux over night. After evaporation of the MeOH, the aqueous phase is extracted with ethylacetate, acidified with 2N HCl, and extracted again with ethylacetate. This second extract is evaporated yielding 4.2 g of crude 6-(2-methyl-1-oxo-1,2,3,4-tetrahydro-naphthalen-2-yl)-hexanoic acid (4a). In an analogous manner to that described for the conversion of 3b to 3c in example 3, 4a is converted to the title compound 4c. 4c is an oil MS (APCI): 288.1 (M−1). The enantiomers of 4c were separated by semipreparative HPLC using a Chiracel OJ-R and water/methanol as the mobile phase. Purity was determined by analytical HPLC (Chiracel OJ-R column [15 cm, 4.6 mm, particle size 5 μm] using water 40/ methanol 60 v/v at a flow rate of 0.6 ml/min, injection of 10 μl-samples). Retention time and % ee of each enantiomer was 16.75 min (100% ee) and 20.25 min (87% ee), respectively.

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