海萝胶 → 3-{[{[5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}(methoxycarbonyl)amino]methyl}-5-(trifluoromethyl)benzoic acid

HRID 17075

反应方程式

HRID 17075 反应方程式
[CH3:1][O:2][C:3](=[O:40])[N:4]([CH2:27][C:28]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([CH:38]=[O:39])[CH:29]=1)[CH2:5][C:6]1[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:9]=[CH:8][C:7]=1[C:16]1[CH:21]=[C:20]([CH:22]([CH3:24])[CH3:23])[CH:19]=[CH:18][C:17]=1[O:25][CH3:26].CC(=CC)C.[O-:46]Cl=O.[Na+].Cl>C1COCC1.O.CCOC(C)=O.C(O)(C)(C)C>[CH:22]([C:20]1[CH:19]=[CH:18][C:17]([O:25][CH3:26])=[C:16]([C:7]2[CH:8]=[CH:9][C:10]([C:12]([F:15])([F:14])[F:13])=[CH:11][C:6]=2[CH2:5][N:4]([CH2:27][C:28]2[CH:29]=[C:30]([CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=2)[C:38]([OH:46])=[O:39])[C:3]([O:2][CH3:1])=[O:40])[CH:21]=1)([CH3:24])[CH3:23]

参与物

9

反应物 4

HCID 313海萝胶HCID 105532-甲基-2-丁烯HCID 11497822Methyl[3-formyl-5-(trifluoromethyl)benzyl]{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamateHCID 23668197亚氯酸钠

产物 1

HCID 115560893-{[{[5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}(methoxycarbonyl)amino]methyl}-5-(trifluoromethyl)benzoic acid

试剂、催化剂与溶剂 4

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 6386叔丁醇溶剂HCID 8028四氢呋喃溶剂HCID 8857乙酸乙酯溶剂

实验过程

To a solution of methyl[3-formyl-5-(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (37.0 mg, 0.065 mmol) (Example 40) in THF (123 μL) was added t-butanol (360 μL), 2-methyl 2-butene (123 μL), and a solution of NaClO2 (12.9 mg, 0.014 mmol) and NaH2PO4 (19.7 mg, 0.014 mmol) in H2O (152 μL). The reaction was stirred vigorously for two hours at room temperature, diluted with EtOAc (30 mL), and poured into 1N HCl (10 mL). The aqueous layer was extracted with EtOAc (3×20 mL) and the combined organic extracts were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 0.1% acetic acid in 8% MeOH/CH2Cl2 afforded 3-{[{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}(methoxycarbonyl)amino]methyl}-5-(trifluoromethyl)benzoic acid. Rf=0.35 (10% MeOH/CH2Cl2). LCMS=584.3 (M+1)+. 1H NMR (C6D6, 500 MHz, 70° C.) δ 8.28 (broad singlet, 1H), 8.04 (broad singlet, 1H), 7.68 (broad singlet, 1H), 7.37-7.34 (m, 2H), 7.07-7.05 (m, 2H), 6.87 (s, 1H), 6.62 (d, J=8.0 Hz, 1H), 4.43 (broad singlet, 2H), 4.41 (broad singlet, 2H), 3.40 (s, 3H), 3.29 (s, 3H), 2.75 (m, 1H), 1.17 (d, J=6.5 Hz, 6H).

后处理

  1. extractionThe aqueous layer was extracted with EtOAc (3×20 mL)
  2. washthe combined organic extracts were washed with brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash chromatography with 0.1% acetic acid in 8% MeOH/CH2Cl2

来源与证据

ORD记录
ord-81e4c662273d494088ea9eb338148cce
来源数据集
uspto-grants-2010_06
专利号
US07737295B2

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