Sodium Hydroxide → (E)-3-{1'-tert-butoxycarbonyl-3-oxo-spiro[benzofuran-2(3H), 4'-piperidin]-5-yl}-acrylic acid

Participants

Reaction Steps

(E)-3-{1′-Tert-butoxycarbonyl-3-oxo-spiro[benzofuran-2(3H),4′-piperidin]-5-yl}-acrylic acid methyl ester (100 mg, 0.258 mmol, Intermediate 4, Step E) was hydrolyzed with NaOH following the procedure described in Example 1, Step A, giving (E)-3-{1′-tert-butoxycarbonyl-3-oxo-spiro[benzofuran-2(3H),4′-piperidin]-5-yl}-acrylic acid as a white solid (95 mg, 98%). The product was treated with NH2OTHP according to the procedure described in Example 1, Step B, giving (E)-3-{1′-tert-butoxycarbonyl-3-oxo-spiro[benzofuran-2(3H),4′-piperidin]-5-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide as a yellow solid (89 mg, 74%). Finally, removal of the protecting groups following the procedure described in Example 1, Step C gave (E)-3-{3-oxo-spiro[benzofuran-2(3H),4′-piperidin]-5-yl}-N-hydroxy-acrylamide (14 mg, 23%) as its hydrochloride salt.

Provenance & Evidence