Sodium Hydroxide → (E)-3-{1'-tert-butoxycarbonyl-4-oxo-spiro[chromane-2,4'-piperidine]-7-yl}-acrylic acid

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Reaction Steps

(E)-3-{1′-Tert-butoxycarbonyl-4-oxo-spiro[chromane-2,4′-piperidine]-7-yl}-acrylic acid methyl ester (602 mg, 1.5 mmol, Intermediate 2, Step B) was treated with NaOH following the procedure described in Example 1, Step A, giving (E)-3-{1′-tert-butoxycarbonyl-4-oxo-spiro[chromane-2,4′-piperidine]-7-yl}-acrylic acid as a white solid (560 mg, 96%). The resulting product was treated with NH2OTHP according to the procedure described in Example 1, Step B, giving (E)-3-{1′-tert-butoxycarbonyl-4-oxo-spiro[chromane-2,4′-piperidine]-7-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide as a yellow solid (572 mg, 81%). Finally, removal of the THP and the BOC protecting groups following the procedure described in Example 1, Step C gave (E)-3-{4-oxo-spiro[chromane-2,4′-piperidine]-7-yl}-N-hydroxy-acrylamide (280 mg, 70%) as a yellow solid (hydrochloride salt).

Provenance & Evidence