Benzyl Bromide → (E)-3-{1'-benzyl-3-oxo-spiro[benzofuran-2(3H), 4'-piperidin]-5-yl}-acrylic acid

Participants

Reaction Steps

(E)-3-{1′-Benzyl-3-oxo-spiro[benzofuran-2(3H), 4′-piperidin]-5-yl}-acrylic acid methyl ester was obtained starting from (E)-3-{3-oxo-spiro[benzofuran-2(3H), 4′-piperidin]-5-yl}-acrylic acid methyl ester (247 mg, 0.76 mmol, Intermediate 4) and benzyl bromide, according to the procedure described in Example 2, Step A (280 mg, 98%). The methyl ester was hydrolyzed with NaOH following the procedure described in Example 1, Step A, giving (E)-3-{1′-benzyl-3-oxo-spiro[benzofuran-2(3H), 4′-piperidin]-5-yl}-acrylic acid as a white solid (249 mg, 93%). The resulting acid was treated with NH2OTHP according to the procedure described in Example 1, Step B, giving (E)-3-{1′-benzyl-3-oxo-spiro[benzofuran-2(3H), 4′-piperidin]-5-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide as a yellow solid (62 mg, 20%). Finally, removal of the THP protecting group following the procedure described in Example 1, Step C gave (E)-3-{1′-benzyl-3-oxo-spiro[benzofuran-2(3H), 4′-piperidin]-5-yl}-N-hydroxy-acrylamide as its hydrochloride salt (30 mg, 50%).

Provenance & Evidence