Sodium Hydroxide → (E)-3-{1'-tert-butoxycarbonyl-3-oxo-spiro[benzofuran-2(3H), 4'-piperidin]-5-yl}-acrylic acid
Reaction equation
C[O:2][C:3](=[O:28])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[CH:8][C:9]2[O:25][C:12]3([CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[C:11](=[O:26])[C:10]=2[CH:27]=1.[OH-].[Na+]>>[C:21]([O:20][C:18]([N:15]1[CH2:16][CH2:17][C:12]2([C:11](=[O:26])[C:10]3[CH:27]=[C:6](/[CH:5]=[CH:4]/[C:3]([OH:28])=[O:2])[CH:7]=[CH:8][C:9]=3[O:25]2)[CH2:13][CH2:14]1)=[O:19])([CH3:24])([CH3:22])[CH3:23]Participants
Procedure
(E)-3-{1′-Tert-butoxycarbonyl-3-oxo-spiro[benzofuran-2(3H), 4′-piperidin]-5-yl}-acrylic acid methyl ester (100 mg, 0.258 mmol, Intermediate 4, Step E) was hydrolyzed with NaOH following the procedure described in Example 1, Step A, giving (E)-3-{1′-tert-butoxycarbonyl-3-oxo-spiro[benzofuran-2(3H), 4′-piperidin]-5-yl}-acrylic acid as a white solid (95 mg, 98%). The product was treated with NH2OTHP according to the procedure described in Example 1, Step B, giving (E)-3-{1′-tert-butoxycarbonyl-3-oxo-spiro[benzofuran-2(3H), 4′-piperidin]-5-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide as a yellow solid (89 mg, 74%). Finally, removal of the protecting groups following the procedure described in Example 1, Step C gave (E)-3-{3-oxo-spiro[benzofuran-2(3H), 4′-piperidin]-5-yl}-N-hydroxy-acrylamide (14 mg, 23%) as its hydrochloride salt.
Sources & evidence
- ORD record
- ord-2e655d97be9a4f9e80e5b454e8e16af9
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09115148B2
Reaction notes
Loading…