Methyl iodide → (4R,5S)-4-methyl-3-((2R)-2-methyl-4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinone

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Reaction Steps

4,4,4-Trifluorobutyric acid may be converted into 4,4,4-trifluorobutyryl chloride by treatment with oxalyl chloride. The 4,4,4-trifluorobutyryl chloride may then be converted into (4R,5S)-4-methyl-3-(4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinone by reaction with (4R,5S)-(+)-4-methyl-5-phenyl-2-oxazolidinone in the presence of butyl lithium. The product of this reaction may then be methylated by treatment with sodium bis(trimethylsilylamide) followed by methyl iodide to afford (4R,5S)-4-methyl-3-((2R)-2-methyl-4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinone. This product may then be treated with lithium aluminium hydride to afford (R)-2-methyl-4,4,4-trifluorobutan-1-ol. Treatment of this alcohol with phthalimide in the presence of triphenylphosphine and diethyl azodicarboxylate affords (R)-2-(2-methyl-4,4,4-trifluorobutyl)-1H-isoindol-1,3(2H)-dione. Treatment of this product with hydrazine monohydrate followed by hydrochloric acid affords the desired (R)-2-methyl-4,4,4-trifluorobutylamine as the hydrochloride salt.

Provenance & Evidence