(Diethylamino)sulfur trifluoride → 4-[5-(2-Fluoro-ethyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one

HRID 1690751Notes

Reaction equation

HRID 1690751 reaction equation
O[CH2:2][CH2:3][C:4]1[N:8]([CH:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:19])[O:11][C:10]2([CH3:21])[CH3:20])[CH:7]=[N:6][CH:5]=1.CCN(S(F)(F)[F:28])CC>ClCCl>[F:28][CH2:2][CH2:3][C:4]1[N:8]([CH:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:19])[O:11][C:10]2([CH3:21])[CH3:20])[CH:7]=[N:6][CH:5]=1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 577811284-[5-(2-Hydroxyethyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one

Product 1

HCID 577811274-[5-(2-Fluoro-ethyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a partial suspension of 4-[5-(2-hydroxy-ethyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one (0.180 g, 0.616 mmol) (example 27f) in dichloromethane (10 mL) at 0° C. under nitrogen is added DAST (0.314 g, 1.848 mmol) dropwise. After 30 min, the mixture is diluted with dichloromethane and 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-(2-fluoro-ethyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one as an oil. The material is converted to the HCl salt and triturated with methanol, to give a crystalline solid; MS (ESI) m/z 289.0 (M+H); 1H NMR (400 MHz, MeOD) δ ppm 1.27 (s, 3 H), 1.59 (s, 3 H), 4.69-4.95 (m, 4 H), 5.73 (br. S., 1 H), 7.16 (s, 1 H), 7.53 (d, J=7.6 Hz, 1 H), 7.63 (br. S., 1 H), 7.71 (td, J=7.6, 1.1 Hz, 1 H), 7.81 (td, J=7.6, 1.3 Hz, 1H), 8.27 (dd, J=7.8, 1.3 Hz, 1 H).

Workup

  1. washwashed 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)

Sources & evidence

ORD record
ord-d6243accf20e45d69f808f216e904f3d
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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