p-Toluenesulfonic acid → 2-{[4-fluoro-2'-(iodomethyl)-5-isopropyl-4'-(trifluoromethyl)biphenyl-2-yl]oxy}tetrahydro-2H-pyran

HRID 1028624

Reaktionsgleichung

Reaktionsgleichung von HRID 1028624
C1(C)C=CC(S(O)(=O)=O)=CC=1.[F:12][C:13]1[CH:14]=[C:15]([OH:34])[C:16]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][C:23]=2[CH2:32][I:33])=[CH:17][C:18]=1[CH:19]([CH3:21])[CH3:20].[O:35]1[CH:40]=[CH:39][CH2:38][CH2:37][CH2:36]1>C(Cl)Cl.C([O-])(O)=O.[Na+]>[F:12][C:13]1[C:18]([CH:19]([CH3:21])[CH3:20])=[CH:17][C:16]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][C:23]=2[CH2:32][I:33])=[C:15]([O:34][CH:36]2[CH2:37][CH2:38][CH2:39][CH2:40][O:35]2)[CH:14]=1

Komponenten

6

Edukt 3

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 667166694-Fluoro-2'-(iodomethyl)-5-isopropyl-4'-(trifluoromethyl)biphenyl-2-ol

Produkt 1

HCID 667166702-{[4-fluoro-2'-(iodomethyl)-5-isopropyl-4'-(trifluoromethyl)biphenyl-2-yl]oxy}tetrahydro-2H-pyran

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

p-Toluenesulfonic acid (2.8 mg, 0.0145 mmol) was added to a solution of 4-fluoro-2′-(iodomethyl)-5-isopropyl-4′-(trifluoromethyl)biphenyl-2-ol (63.4 mg, 0.145 mmol) and 3,4-dihydro-2H-pyran (60.8 mg, 66 μL, 0.723 mmol) in dry CH2Cl2 (7.2 mL) at room temperature under N2 and the reaction was stirred for 3 days. The reaction mixture was diluted with saturated NaHCO3 (20 mL) and extracted with CH2Cl2 (3×20 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 12×160 mm, 0-20% EtOAc in hexanes gradient) to afford 2-{[4-fluoro-2′-(iodomethyl)-5-isopropyl-4′-(trifluoromethyl)biphenyl-2-yl]oxy}tetrahydro-2H-pyran. Rf=0.74 (10% EtOAc in hexanes). 1H NMR (500 MHz, CDCl3) δ 7.75 (s, 1H), 7.62 (d, J=8.3 Hz, 0.5H), 7.59 (d, J=8.3 Hz, 0.5H), 7.53 (t, J=7.3 Hz, 0.5H), 7.41 (s, 0.5H), 7.32 (d, J=7.9 Hz, 0.5H), 7.25 (d, J=7.9 Hz, 0.5H), 7.15 (t, J=9.4 Hz, 0.5H), 6.99 (d, J=12.2 Hz, 0.5H), 6.94 (d, J=12.2 Hz, 0.5H), 6.69 (d, J=11.0 Hz, 0.5H), 5.37 (s, 0.5H), 5.23 (s, 0.5H), 5.13 (s, 1H), 4.45 (d, J=9.6 Hz, 0.5H), 4.40 (d, J=9.6 Hz, 0.5H), 4.31 (d, J=9.6 Hz, 0.5H), 4.23 (d, J=9.6 Hz, 0.5H) 3.76 (m, 0.5H), 3.66-3.54 (m, 1.5H), 3.29-3.21 (m, 1H), 1.68-1.44 (m, 4H) 1.32-1.26 (m, 6H).

Aufarbeitung

  1. extractionextracted with CH2Cl2 (3×20 mL)
  2. dry with materialThe combined extracts were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customto give the crude product
  5. customThis was purified by flash chromatography (Si, 12×160 mm, 0-20% EtOAc in hexanes gradient)

Quellen und Nachweise

ORD-Eintrag
ord-4b50fc2ea8c54dbba424772320f65c2b
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08735435B2

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