Trimethylsilyl iodide → (3s,5Rs)-1-(4-chloro-quinolin-7-ylmethyl)-3,5-dimethyl-piperazin-2-one

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Reaction Steps

(2S, 6RS)-4-(4-Chloro-quinolin-7-ylmethyl)-2,6-dimethyl-3-oxo-piperazine-1-carboxylic acid benzyl ester (417 mg, 1.0 mmol) is taken up in 7 mL of acetonitrile, and iodotrimethyl-silane (0.43 mL, 3.0 mmol) is added. The resulting mixture is stirred for one hour at room temperature before quenched with methanol (1 mL). The residue after concentration is taken up in 2N hydrochloric acid (3 mL) and is extracted with ether (2×30 mL). The aqueous layer is condensed to dryness and the residue is recrystalized from isopropanol and ether to give a mixture (1:4 ratio) of (3S, 5RS)-1-(4-chloro-quinolin-7-ylmethyl)-3,5-dimethyl-piperazin-2-one as a yellow solid (290 mg). The two epimers are separated using a flash column (SiO2, 1% triethylamine/3% methanol/methylene chloride). C16H18ClN3O MS m/z: 304, 306. The minor isomer (3S, 5R)-1-(4-chloro-quinolin-7-ylmethyl)-3,5-dimethyl-piperazin-2-one.is (3S, 5R)-1-(4-chloro-quinolin-7-ylmethyl)-3,5-dimethyl-piperazin-2-one while the major isomer is (3S, 5S)-1-(4-chloro-quinolin-7-ylmethyl)-3,5-dimethyl-piperazin-2-one. Alternatively, (3S, 5R)-1-(4-chloro-quinolin-7-ylmethyl)-3,5-dimethyl-piperazin-2-one and (3S, 5S)-1-(4-chloro-quinolin-7-ylmethyl)-3,5-dimethyl-piperazin-2-one can be made via the same chemistry shown below from pure (2S, 6S)-2,6-dimethyl-3-oxo-piperazine-1-carboxylic acid benzyl ester and (2S, 6RS)-4-(4-chloro-quinolin-7-ylmethyl)-2,6-dimethyl-3-oxo-piperazine-1-carboxylic acid benzyl ester, respectively.

Provenance & Evidence