反応式
N#N.[CH3:3][O:4][C:5](=[O:36])[CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[NH:19][C:20](=[O:35])[CH2:21][CH2:22][C:23]2[CH:28]=[C:27]([O:29]C)[C:26]([O:31]C)=[C:25]([O:33]C)[CH:24]=2)[CH:10]=[CH:11][CH:12]=1.B(Br)(Br)Br>C(Cl)Cl>[CH3:3][O:4][C:5](=[O:36])[CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[NH:19][C:20](=[O:35])[CH2:21][CH2:22][C:23]2[CH:24]=[C:25]([OH:33])[C:26]([OH:31])=[C:27]([OH:29])[CH:28]=2)[CH:10]=[CH:11][CH:12]=1参加物
反応条件
- 温度
- -78 °C
実験手順
(The following reaction is done in an anhydrous N2 atmosphere.) Dissolve {2′-[3-(3,4,5-Trimethoxy-phenyl)-propionylamino]-biphenyl-3-yl}-acetic acid methyl ester (72) (46 mg, 0.10 mmol) in anhydrous DCM (1.0 mL), cool the solution to −78° C. and add dropwise BBr3 (85 μL, 0.90 mmol). Stir the reaction mixture for 30 min at −78° C. and after slowly warming up for additional 2 h at rt. Add dropwise ice water, separate layers and extract aqu. layer with DCM (3 times). Wash combined organic layer with brine and dry with Na2SO4. Purify the crude product by preparative RP HPLC (gradient, water/CH3CN 95:5 to 5:95) to obtain {2′-[3-(3,4,5-Trihydroxy-phenyl)-propionylamino]-biphenyl-3-yl}-acetic acid methyl ester (73) (2 mg, 5%). 1H NMR (400 MHz, CD3CN): 2.43 (t, 2H, J=7.6 Hz); 2.69 (t, 2H, J=7.6 Hz); 3.66 (s, 3H); 3.70 (s, 2H); 6.25 (s, 2H); 7.18-7.34 (m, 5 H); 7.35-7.44 (m, 2H); 7.65 (br.s, 1H); 7.89 (br.d, 1H, J=8.3 Hz).
後処理
- custom(The following reaction
- temperatureafter slowly warming up for additional 2 h at rt
- customseparate layers
- extractionextract aqu
- washWash
- dry with materialdry with Na2SO4
- customPurify the crude product by preparative RP HPLC (gradient, water/CH3CN 95:5 to 5:95)
出典と根拠
- ORDレコード
- ord-a9dcd5bfeff7454cb3cd57ea2b25269b
- 出典データセット
- uspto-grants-2013_02
- 特許番号
- US08367677B2
関連ノート
読み込み中…