Reacción #605412

Ecuación de reacción

(E)-3-{1′-Tert-butoxycarbonyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester

(E)-3-{1′-tert-butoxycarbonyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester

NaOH

citric acid

→

(E)-3-{1′-tert-butoxycarbonyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid

Rendimiento 99.2%

Condiciones de reacción

Procedimiento

(E)-3-{1′-Tert-butoxycarbonyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester (obtained as described in Example 25, Step A, 300 mg, 0.745 mmol) was treated with 1 M NaOH following the procedure described in Example 71, Step B, using citric acid instead of hydrochloric acid giving (E)-3-{1′-tert-butoxycarbonyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid (287 mg, 99%). The resulting product was treated with NH2OTHP according to the procedure described in Example 71, Step C, giving (E)-3-{1′-tert-butoxycarbonyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide. Finally, removal of the THP and BOC protecting groups following the procedure described in Example 71, Step C gave (E)-3-{3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-N-hydroxy-acrylamide hydrochloride (109 mg) as a white solid.

Fuente