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

HRID 17075

反応式

HRID 17075 の反応式
[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]

参加物

9

反応物 4

HCID 313Hydrochloric AcidHCID 105532-Methyl-2-buteneHCID 11497822Methyl[3-formyl-5-(trifluoromethyl)benzyl]{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamateHCID 23668197Sodium Chlorite

生成物 1

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

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 6386tert-Butanol溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-81e4c662273d494088ea9eb338148cce
出典データセット
uspto-grants-2010_06
特許番号
US07737295B2

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