Benzyl Bromide → (E)-3-{1'-benzyl-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](OC(C)(C)C)=O)[CH2:14][CH2:13]3)[C:11](=[O:26])[C:10]=2[CH:27]=1.C(Br)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[OH-].[Na+]>>[CH2:18]([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:2])=[O:28])[CH:7]=[CH:8][C:9]=3[O:25]2)[CH2:13][CH2:14]1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1Participants
Procedure
(E)-3-{1′-Benzyl-3-oxo-spiro[benzofuran-2(3H), 4′-piperidin]-5-yl}-acrylic acid methyl ester was obtained starting from (E)-3-{3-oxo-spiro[benzofuran-2(3H), 4′-piperidin]-5-yl}-acrylic acid methyl ester (247 mg, 0.76 mmol, Intermediate 4) and benzyl bromide, according to the procedure described in Example 2, Step A (280 mg, 98%). The methyl ester was hydrolyzed with NaOH following the procedure described in Example 1, Step A, giving (E)-3-{1′-benzyl-3-oxo-spiro[benzofuran-2(3H), 4′-piperidin]-5-yl}-acrylic acid as a white solid (249 mg, 93%). The resulting acid was treated with NH2OTHP according to the procedure described in Example 1, Step B, giving (E)-3-{1′-benzyl-3-oxo-spiro[benzofuran-2(3H), 4′-piperidin]-5-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide as a yellow solid (62 mg, 20%). Finally, removal of the THP protecting group following the procedure described in Example 1, Step C gave (E)-3-{1′-benzyl-3-oxo-spiro[benzofuran-2(3H), 4′-piperidin]-5-yl}-N-hydroxy-acrylamide as its hydrochloride salt (30 mg, 50%).
Sources & evidence
- ORD record
- ord-019f0eadc1d84f1b8d6c0c911873245f
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09115148B2
Reaction notes
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