Hydrazine hydrate (1:1) → (2S)-N-((1R)-2-amino-1-[4-((S)-2-methylbutoxy)phenyl]-ethyl)-2-phenylpropionamide

Participants

Reaction Conditions

Reaction Steps

A mixture of (S)-N-((R)-2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-1-(4-((S)-2-methyl-butoxy)-phenyl)-ethyl)-2-phenyl-propionamide (320 mg, 0.66 mmol) and ethanol (20 mL) was treated dropwise with hydrazine monohydrate (0.32 mL, 6.6 mmol), and the resulting reaction was maintained at 60° C. overnight. The mixture was allowed to cool to room temperature and the solids were removed by filtration. The filtrate was concentrated to dryness, and triturated with ethyl acetate (15 mL), and the mixture was filtered. The collected solids were air dried, then dissolved in diethyl ether (5 mL). The resulting solution was treated with concentrated HCl (0.05 mL), and the precipitate was collected by filtration to afford (2S)-N-((1R)-2-amino-1-[4-((S)-2-methylbutoxy)phenyl]-ethyl)-2-phenylpropionamide (120 mg, 52% yield) as a white solid: 1H NMR (400 MHz, MeOD) δ 7.21-7.31 (m, 5H), 7.09 (d, J=8.6 Hz, 2H), 6.84 (d, J=8.8 Hz, 2H), 5.12 (dd, J=8.8, 5.8 Hz, 1H), 3.81 (dd, J=9.3, 6.1 Hz, 1H), 3.70-3.77 (m, 2H), 3.23-3.30 (m, 2H), 1.81 (s, 1H), 1.57 (ddd, J=13.4, 7.6, 5.8 Hz, 1H), 1.47 (d, J=6.8 Hz, 3H), 1.24-1.33 (m, 1H), 1.02 (d, J=6.8 Hz, 3H), 0.96 (t, J=7.5 Hz, 3H); LRMS (ESI) m/e 355.1 [(M+H)+, calcd for C22H31N2O2 355.5].

Provenance & Evidence