Pivaloyl chloride → N-(N-(N-(N-(2,2-dimethylpropionyl)-L-alanyl)-L-alanyl)-L-prolyl)-L-valine [11beta,21-dihydroxy-3,20-dioxo-6alpha-methyl-17-propionyloxy-pregna-1,4-dien-21-yl] ester

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Reaction Steps

150 mg (0.17 mmol) of H-Ala-Ala-Pro-Val-O-MPP x TFA (Example 3) and 60 μl (0.34 mmol) of diisopropylethylamine are dissolved in 6 ml of dichloromethane, mixed with 20 μl (0.18 mmol) of pivaloyl chloride and stirred for 25 hours at room temperature. The residue that remains after removal of the solvent i.vac. is directly chromatographed. Gradient chromatography (24 g of silica gel 60, hexane→hexane/acetone 7:3) yields 102 mg (70%) of slightly contaminated N-(N-(N-(N-(2,2-dimethylpropionyl)-L -alanyl)-L-alanyl)-L-prolyl)-L-valine [11β,21-dihydroxy-3,20-dioxo-6α-methyl-17-propionyloxy-pregna-1,4-dien-21-yl] ester. A second chromatography (Lichroprep Si60A pre-packed column, hexane/dichloromethane 1:1→hexane/dichloromethane/methanol 30:60:10) yields 92 mg, 83 mg of crystalline compound consisting of dichloromethane/diisopropyl ether.

Provenance & Evidence