Imidazole → Tert-butyl{[4'-fluoro-5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methoxy}dimethylsilane

HRID 1028626Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1028626
[Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N1C=CN=C1.[F:14][C:15]1[C:20]([CH:21]([CH3:23])[CH3:22])=[CH:19][C:18]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][C:25]=2[CH2:34][OH:35])=[C:17]([O:36][CH3:37])[CH:16]=1.O>C(Cl)Cl>[C:4]([Si:1]([O:35][CH2:34][C:25]1[CH:26]=[C:27]([C:30]([F:32])([F:33])[F:31])[CH:28]=[CH:29][C:24]=1[C:18]1[CH:19]=[C:20]([CH:21]([CH3:23])[CH3:22])[C:15]([F:14])=[CH:16][C:17]=1[O:36][CH3:37])([CH3:3])[CH3:2])([CH3:7])([CH3:6])[CH3:5]

Komponenten

6

Edukt 4

HCID 795ImidazoleHCID 962WaterHCID 28928tert-Butyldimethylsilyl chlorideHCID 533638284'-Fluoro-2'-methoxy-5'-(1-methylethyl)-4-(trifluoromethyl)(1,1'-biphenyl)-2-methanol

Produkt 1

HCID 66717161Tert-butyl{[4'-fluoro-5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methoxy}dimethylsilane

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

tert-Butyldimethylsilyl chloride (0.48 g, 3.21 mmol) and imidazole (0.50 g, 7.30 mmol) were added successively to a stirred solution of [4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanol (1.00 g, 2.93 mmol) in dry CH2Cl2 (13.4 mL) at room temperature under N2 and the reaction was stirred overnight. Water (50 mL) was added and the mixture was extracted with EtOAc (3×50 mL). The combined extracts were dried (MgSO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 25×160 mm, 1% EtOAc in hexanes) to afford tert-butyl {[4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methoxy}dimethylsilane as a colorless oil. Rf=0.16 (1% EtOAc in hexanes). LCMS calc.=457.2; found=457.2 (M+1)+. 1H NMR (500 MHz, CDCl3) δ 7.94 (s, 1H), 7.57 (d, J=7.8 Hz, 1H), 7.29 (d, J=7.6 Hz, 1H), 7.00 (d, J=8.6 Hz, 1H), 6.69 (d, J=12.1 Hz, 1H), 4.63 (br s, 1H), 4.50 (br s, 1H), 3.75 (s, 3H), 3.29-3.21 (m, 1H), 1.28 (d, J=6.9 Hz, 6H), 0.93 (s, 9H), 0.03 (s, 6H).

Aufarbeitung

  1. extractionthe mixture was extracted with EtOAc (3×50 mL)
  2. dry with materialThe combined extracts were dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customto give the crude product
  5. customThis was purified by flash chromatography (Si, 25×160 mm, 1% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-04f0f67e5b6b4c409f927da08971b42f
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08735435B2

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