Diethylamine → Atreleuton

Participants

Reaction Steps

To a solution of 2-iodo-5-(4-fluorophenylmethyl)thiophene (5.30 g, 16.6 mmol), prepared as in step 2, in anhydrous DMF (5.0 mL) was added (R)-N-hydroxy-N-(3-butyn-2-yl)urea (2.12 g, 16.6 mmol), triphenylphosphine (84 mg, 0.32 mmol), bis(acetonitrile)palladium(II) chloride (40 mg, 0.16 mmol), copper (I) iodide (16 rag, 0.08 mmol), and diethylamine (5.6 ml). The mixture was stirred under nitrogen at ambient temperature for 22 hours and concentrated in vacuo at 32° C. The residue was subjected to chromatography on silica eluting with 2-7% MeOH in CH2Cl2, crystallization from ethyl acetate-hexane and trituration in CH2Cl2 to afford (R)-N-{3-[5-(4-fluorophenylmethyl)thien-2-yl]-1-methyl-2-propynyl}-N-hydroxyurea as a cream-colored solid 0.94 g (18%). m.p. 135°-136° C.(dec). 1H NMR (DMSO-d6, 300 MHz) δ1.32 (d, J=6.0 Hz, 3H), 4.11 (s, 2H), 5.10 (q, J=6.0Hz, 1H), 6.54 (s, 2H), 6.81 (d, J=3.0Hz, 1H), 7.08 (d, J=3.0Hz, 1H), 7.10-7.18 (m, 2H), 7.25-7.32 (m, 2H), 9.33 (s, 1H). MS (DCI/NH3) m/e 319 (M+H)+. [a]D23° =+47.8° (C=1, MeOH). Anal calcd for C16H15FN2O2S: C, 60.36; H, 4.75; N, 8.80. Found: C, 60.31; H, 4.79; N, 8.50.

Provenance & Evidence