Sodium Hydroxide → (E)-3-{1'-phenyl-4-oxo-spiro[chromane-2,4'-piperidine]-6-yl}-acrylic acid
Reaction equation
C[O:2][C:3](=[O:28])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:24](=[CH:25][CH:26]=1)[O:23][C:11]1([CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:13][CH2:12]1)[CH2:10][C:9]2=[O:27].[OH-].[Na+]>>[C:17]1([N:14]2[CH2:15][CH2:16][C:11]3([CH2:10][C:9](=[O:27])[C:8]4[C:24](=[CH:25][CH:26]=[C:6](/[CH:5]=[CH:4]/[C:3]([OH:28])=[O:2])[CH:7]=4)[O:23]3)[CH2:12][CH2:13]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1Participants
Procedure
(E)-3-{1′-Phenyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (541 mg, 1.43 mmol) was hydrolyzed with NaOH following the procedure described in Example 1, Step A, giving (E)-3-{1′-phenyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid as a white solid (455 mg, 87%). The resulting product was treated with NH2OTHP according to the procedure described in Example 1, Step B, giving (E)-3-{1′-phenyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide as a yellow solid (393 mg, 69%). Finally, the removal of the THP protecting group following the procedure described in Example 2, Step D gave the crude product, which was purified by preparative HPLC giving 50 mg of (E)-3-{1′-phenyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-hydroxy-acrylamide as its trifluoro acetic salt.
Sources & evidence
- ORD record
- ord-59b2a6fa81914f7c808bb836ae50bbee
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09115148B2
Reaction notes
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