(Diethylamino)sulfur trifluoride → 4-(5-Fluoromethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one

HRID 1690737

Reaktionsgleichung

Reaktionsgleichung von HRID 1690737
O[CH2:2][C:3]1[N:7]([CH:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](=[O:18])[O:10][C:9]2([CH3:20])[CH3:19])[CH:6]=[N:5][CH:4]=1.CCN(S(F)(F)[F:27])CC>ClCCl>[F:27][CH2:2][C:3]1[N:7]([CH:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](=[O:18])[O:10][C:9]2([CH3:20])[CH3:19])[CH:6]=[N:5][CH:4]=1

Komponenten

4

Edukt 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 577811224-(5-Hydroxymethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one

Produkt 1

HCID 248051714-(5-Fluoromethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 4-(5-hydroxymethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one (0.158 g, 0.574 mmol) (Example 6d) in dichloromethane (7 mL) at 0° C. under nitrogen is added DAST (0.487 g, 2.872 mmol) dropwise. The mixture is stirred at 0° C. overnight. After dilution with dichloromethane, the organic phase is washed twice with saturated aqueous sodium bicarbonate, water and brine. The combined aqueous phase is back-extracted once with dichloromethane. The combined organic phase is dried over magnesium sulfate and filtered through a cotton plug. The residue is purified by silica gel flash chromatography (elution with dichloromethane-methanol, 99:1 to 49:1) to afford 4-(5-fluoromethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one as a white solid; MS (ESI) m/z 275.0 (M+H); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.31 (s, 3 H), 1.57 (s, 3 H), 5.27 (s, 1 H), 5.45 (dd, J=22.7, 12.4 Hz, 1 H), 5.58 (dd, J=21.2, 12.4 Hz, 1 H), 7.21 (d, J=5.3 Hz, 1 H), 7.29 (d, J=7.3 Hz, 1 H), 7.38 (d, J=2.8 Hz, 1 H), 7.55-7.61 (m, 1 H), 7.65 (dd, J=7.6, 1.5 Hz, 1 H), 8.27 (dd, J=7.7, 1.4 Hz, 1 H).

Aufarbeitung

  1. washAfter dilution with dichloromethane, the organic phase is washed twice with saturated aqueous sodium bicarbonate, water and brine
  2. extractionThe combined aqueous phase is back-extracted once with dichloromethane
  3. dry with materialThe combined organic phase is dried over magnesium sulfate
  4. filtrationfiltered through a cotton plug
  5. customThe residue is purified by silica gel flash chromatography (elution with dichloromethane-methanol, 99:1 to 49:1)

Quellen und Nachweise

ORD-Eintrag
ord-40a88afc5d79484caa635e3fd71eb0b9
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08153674B2

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