Diisopropylamine → 6-Hydroxy-6-(2-methyl-1-oxo-1,2,3,4-tetrahydro-naphtalen-2-yl)-hexanoic acid methyl ester

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Reaction Steps

To 1.55 mL diisopropylamine in 40 mL THF is added a solution of 4.36 mL n-butyllithium (2.5M) in hexane at −78° C. After 10 min, 1.63 g 2-methyl-1-tetralone in 5 mL THF is added, and the solution is stirred for 50 min. Then, 1.60 g 6-oxo-hexanoic acid methyl ester in 5 mL THF is added dropwise, and stirring is continued for 15 min. After that, the cooling bath is removed and the mixture allowed to reach rt. Conc. ammoniachloride sol is added, and extracted with ethylacetate. After evaporation the residue is purified by column chromatography yielding 0.8 g 6-hydroxy-6-(2-methyl-1-oxo-1,2,3,4-tetrahydro-naphtalen-2-yl)-hexanoic acid methyl ester (7a). 2.5 g of this alcohol 8a is dissolved in 50 mL dichloromethane and 2.27 mL triethylamine is added. After cooling to 0° C., 2.86 g methanesulfonic acid anhydride in 20 mL dichloromethane is added dropwise. After complete addition, the cooling bath is removed and stirring continued over night. The solution is washed with 2N HCl and water, separated, dried and evaporated. The crude product and 1.6 g 1,8-diazabicyclo[5.4.0]undecen-7-en (DBU) is dissolved in 60 mL toluene an heated to reflux for 24 h. The mixture is poured on 2N HCl and extracted with dichloromethane. After evaporaton and column chromatography 0.6 g 6-(2-methyl-1-oxo-1,2,3,4-tetrahydro-naphtalen-2-yl)-hex-5-enoic acid methyl ester (7b) is obtained. 7b is converted to 7c in an analogous manner to that described for the conversion of 1c to 1d in example 1. 7c was obtained as an oil, MS (APCI): 286.1 (M−1).

Provenance & Evidence