Triethylamine → (-)-(1S,3S)-4-[3-(tert-butyl-dimethyl-silanyloxy)-cyclopentylamino]-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester

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Reaction Steps

To a solution of (+)-(1S,3S)-(3-azido-cyclopentyloxy)-tert-butyl-dimethyl-silane (580 mg, 2.40 mmol) (from Example 29c supra) in ethanol (30 mL) was added platinum oxide (55 mg, 0.24 mmol) (Aldrich). The mixture was hydrogenated under 1 atmosphere of hydrogen overnight. The reaction mixture was then filtered, the solids were washed with tetrahydrofuran (approximately 30 mL) and the combined filtrate was concentrated to a residue that was dissolved in dioxane (50 mL). To this solution was added triethylamine (970 μL, 705 mg, 6.96 mmol) (Aldrich) and ethyl 4-chloro-2-methylthio-5-pyrimidinecarboxylate (594 mg, 2.55 mmol) (Aldrich) and the mixture was heated at reflux for 45 minutes then cooled and partitioned between ethyl acetate and water. The organic layer was collected, dried over sodium sulfate, filtered and concentrated to a residue that was purified by chromatography on a silica gel column with a 0–20% ethyl acetate in hexanes gradient to give (−)-(1S,3S)-4-[3-(tert-butyl-dimethyl-silanyloxy)-cyclopentylamino]-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester as a colorless viscous oil. (Yield 910 mg, 95%).

Provenance & Evidence