Sodium Hydroxide → (E)-3-{1'-tert-butoxycarbonyl-3,4-dihydro-3-benzyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4'-piperidin]-6-yl}-acrylic acid
Reaction equation
C[O:2][C:3](=[O:36])/[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)[N:12]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:11](=[O:34])[C:10]=2[CH:35]=1.[OH-].[Na+]>>[C:22]([O:21][C:19]([N:16]1[CH2:17][CH2:18][C:13]2([N:12]([CH2:27][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:11](=[O:34])[C:10]3[CH:35]=[C:6](/[CH:5]=[CH:4]/[C:3]([OH:36])=[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 2
Product 1
Procedure
(E)-3-{1′-tert-butoxycarbonyl-3,4-dihydro-3-benzyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester (800 mg, 1.63 mmol, Intermediate 6, Step A) was hydrolyzed with NaOH following the procedure described in Example 1, Step A, to give (E)-3-{1′-tert-butoxycarbonyl-3,4-dihydro-3-benzyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid as a white solid (750 mg, 96%). The resulting product was treated with NH2OTHP according to the procedure described in Example 1, Step B, obtaining (E)-3-{1′-tert-butoxycarbonyl-3,4-dihydro-3-benzyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide as a white solid (430 mg, 48%). Finally, removal of the THP and BOC protecting groups (420 mg, 0.73 mmol) following the procedure described in Example 1, Step C gave (E)-3-{3,4-dihydro-3-benzyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-N-hydroxy-acrylamide (208 mg, trifluoroacetate salt) after purification by preparative HPLC.
Sources & evidence
- ORD record
- ord-6c20a62d730545abb2cc9b0c05f001e3
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09115148B2
Reaction notes
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