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

Participants

Reaction Steps

(E)-3-{1′-tert-butoxycarbonyl-3,4-dihydro-3-benzyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester (800 mg, 1.63 mmol, Intermediate 6, Step A) was hydrolyzed with NaOH following the procedure described in Example 1, Step A, to give (E)-3-{1′-tert-butoxycarbonyl-3,4-dihydro-3-benzyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid as a white solid (750 mg, 96%). The resulting product was treated with NH2OTHP according to the procedure described in Example 1, Step B, obtaining (E)-3-{1′-tert-butoxycarbonyl-3,4-dihydro-3-benzyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide as a white solid (430 mg, 48%). Finally, removal of the THP and BOC protecting groups (420 mg, 0.73 mmol) following the procedure described in Example 1, Step C gave (E)-3-{3,4-dihydro-3-benzyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-N-hydroxy-acrylamide (208 mg, trifluoroacetate salt) after purification by preparative HPLC.

Provenance & Evidence