Diisopropylethylamine → Methyl 2-(3-cyclohexyl-1,1,1-trifluoro-3-nitropropan-2-ylamino)-3,3-dimethylbutanoate

Participants

Reaction Conditions

Reaction Steps

A mixture of (3,3,3-trifluoro-1-nitroprop-1-enyl)cyclohexane (3) (0.62 gm), (S)-methyl 2-amino-3,3-dimethylbutanoate (4) (0.656 gm, 1.3 eq) and diisopropylethylamine (0.69 mL) in toluene (15 mL) was heated to 100° C. for 23 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate, and washed successively with 1N hydrochloric acid, water, brine and then dried over anhydrous sodium sulfate. Evaporation to dryness under reduced pressure gave crude methyl 2-(3-cyclohexyl-1,1,1-trifluoro-3-nitropropan-2-ylamino)-3,3-dimethylbutanoate as a mixture of isomers. Separation by silica gel chromatography, eluting with 8% ethyl acetate/hexane, gave two fractions, a faster eluting compound, 5A-1 (0.553 gm) and a slower eluting compound, 5B-1 (0.3 gm). The two compounds are different diastereoisomers of methyl 2-(3-cyclohexyl-1,1,1-trifluoro-3-nitropropan-2-ylamino)-3,3-dimethylbutanoate (5), although the absolute stereochemistry has not yet been established.

Provenance & Evidence