Citric Acid → (E)-3-{1'-tert-butoxycarbonyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4'-piperidin]-6-yl}-acrylic acid
Reaction equation
C[O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[CH:8][C:9]2[O:26][C:13]3([CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)[NH:12][C:11](=[O:27])[C:10]=2[CH:28]=1.[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>>[C:22]([O:21][C:19]([N:16]1[CH2:17][CH2:18][C:13]2([NH:12][C:11](=[O:27])[C:10]3[CH:28]=[C:6](/[CH:5]=[CH:4]/[C:3]([OH:29])=[O:2])[CH:7]=[CH:8][C:9]=3[O:26]2)[CH2:14][CH2:15]1)=[O:20])([CH3:25])([CH3:23])[CH3:24]Participants
Reactant 3
Product 1
Procedure
(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.
Sources & evidence
- ORD record
- ord-eeb79b1c0b2a43a091713fe3ebc72da1
- Source dataset
- uspto-grants-2013_11
- Patent number
- US08592444B2
Reaction notes
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