Diisobutylaluminum hydride → E-N-[3-(5-(4-Fluorophenylmethyl)-thien-2-yl)-1-(R)-methyl-2-propenyl]-N-hydroxyurea

Participants

Reaction Steps

To a solution of (R)-N-{3-[5-(4-fluorophenylmethyl)thien-2-yl]-1-methyl-2-propynyl}-N-hydroxyurea (0.316g, 1.05 mmol), prepared as in Example 1, step 4, in THF (8 mL) at -70° C. was added DIBAL (5.23 mL, 5.25 mmol). The reaction was slowly allowed to warm to ambient temperature over 17 hours. The reaction was quenched into an aqueous 1M H3PO4 solution and extracted with ethyl acetate. The combined organic layers were washed with aqueous NaHCO3, dried (MgSO4) and evaporated. The residue was purified by chromatography on silica gel (50% ethyl acetate/hexanes/1% acetic acid). The resulting solid was crystallized from hot ethyl acetate/hexanes to yield 0.063 g (20% ) of E-N-[3-(5-(4-Fluorophenylmethyl)-thien-2-yl)-1-(R)-methyl-2-propenyl]-N-hydroxyurea. m.p. 143°-4° C). MS (DCI/NH3) m/e 321 (M+H)+, 338 (M+NH4)+. 1H NMR (DMSO-d6, 300 MHz) δ1.17(d, J=7.2 Hz, 3H), 4.08 (s, 2H), 4.73 (m, 1H), 5.88 (dd, J=6.3, 15.6 Hz, 1H), 6.33 (s, 2H), 6.55 (d, J=15.6 Hz, 1H), 6.77 (d, J=4.2 Hz, 1H), 6.83 (d, J=4.2 Hz, 1H), 7.12 (m, 2H), 7.29 (m, 2H), 9.02 (s, 1H). Anal Calcd for C17H17FN2O2S: C, 59.98; H, 5.35; N, 8.74. Found C, 60.15; H, 5.11; N, 8.75.

Provenance & Evidence