1,1'-Carbonyldiimidazole → (3R)-3-(3-ethoxy-4-methoxyphenyl)-N-hydroxy-3-(1-oxoisoindolinyl)propionamide
Reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C@H:12]([N:17]2[CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]2=[O:26])[CH2:13][C:14](O)=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[NH2:40][OH:41]>O1CCCC1>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C@H:12]([N:17]2[CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]2=[O:26])[CH2:13][C:14]([NH:40][OH:41])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
(3R)-3-(3-Ethoxy-4-methoxyphenyl)-N-hydroxy-3-(1-oxoisoindolinyl)propionamide was prepared by the procedure of Example 1 from (3R)-3-(3-ethoxy-4-methoxyphenyl)-3-(1-oxoisoindolinyl)propanoic acid (3.48 g, 9.79 mmol), carbonyldiimidazole (1.91 g, 11.8 mmol) and hydroxylamine hydrochloride (0.95 g, 13.7 mmol) in tetrahydrofuran (10 mL) to afford (3R)-3-(3-ethoxy-4-methoxyphenyl)-N-hydroxy-3-(1-oxoisoindolinyl)propionamide as a white solid (2.4 g, 69% yield): mp, 183.5–184.5° C.; 1H NMR (DMSO-d6) δ 1.29 (t, J=6.9 Hz, 3H, CH3) 2.81–2.86 (m, 2H, CH2), 3.72 (s, 3H, CH3), 3.96–4.04 (m, 2H, CH2), 4.13 (d, J=17.5 Hz, 1H, CHH), 4.54 (d, J=17.5 Hz, 1H, NCHH), 5.73 (t, J=7.9 Hz, 1H, NCH), 6.84–6.92 (m, 3H, Ar), 7.43–7.68 (m, 4H, Ar), 8.83 (br.s, 1H, OH), 10.61 (br s, 1H, NH); 13C NMR (DMSO-d6) δ 14.68, 35.04, 46.22, 51.20, 55.44, 63.73, 111.85, 112.19, 119.21, 122.78, 123.43, 127.83, 131.29, 131.85, 132.27, 141.67, 147.85, 148.42, 165.99, 166.82. Anal. Calcd for C20H22N2O5: C, 64.85; H, 5.99; N, 7.56. Found: C, 64.82; H, 5.95; N, 7.47.
Sources & evidence
- ORD record
- ord-b5a12aad29b04ed695d6ae3b837538c8
- Source dataset
- uspto-grants-2006_08
- Patent number
- US07091356B2
Reaction notes
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