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

HRID 217518

Reaktionsgleichung

Reaktionsgleichung von HRID 217518
[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]

Komponenten

9

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 6386tert-ButanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-b353a02f2a33410882200fff9db7c514
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193365B2

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