Sodium Hydroxide → (+/-)-(E)-3-{1'-(4-fluoro-benzyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,3'-piperidin]-6-yl}-acrylic acid
Reaction equation
C[O:2][C:3](=[O:30])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[CH:8][C:9]2[O:27][C:13]3([CH2:18][CH2:17][CH2:16][N:15]([CH2:19][C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[CH2:14]3)[NH:12][C:11](=[O:28])[C:10]=2[CH:29]=1.[OH-].[Na+]>O.O1CCOCC1>[F:26][C:23]1[CH:24]=[CH:25][C:20]([CH2:19][N:15]2[CH2:16][CH2:17][CH2:18][C:13]3([NH:12][C:11](=[O:28])[C:10]4[CH:29]=[C:6](/[CH:5]=[CH:4]/[C:3]([OH:30])=[O:2])[CH:7]=[CH:8][C:9]=4[O:27]3)[CH2:14]2)=[CH:21][CH:22]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Procedure
A solution of (±)-(E)-3-{1′-(4-fluoro-benzyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,3′-piperidin]-6-yl}-acrylic acid methyl ester (300 mg, 0.73 mmol) in water (2.5 ml) and dioxane (5 ml) was treated with 1 M NaOH (0.95 ml) as described in Example 30, Step A to give (±)-(E)-3-{1′-(4-fluoro-benzyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,3′-piperidin]-6-yl}-acrylic acid as a white solid [LC-MS: (ES+) MH+: 397]. The obtained acrylic acid was suspended in DCM (5 ml), treated with TEA (0.15 ml, 1.1 mmol) and then with EDC (208 mg, 1.09 mmol), HOBt (147 mg, 1.09 mmol) and NH2OTHP (102 mg, 0.87 mmol) following the procedure described in Example 30, Step B, giving (±)-(E)-3-{t-(4-fluoro-benzyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,3′-piperidin]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide (60 mg) as a light yellow solid.
Sources & evidence
- ORD record
- ord-e2166a6a3921493b805aa4edb4d8d9f4
- Source dataset
- uspto-grants-2015_03
- Patent number
- US08980877B2
Reaction notes
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