Sodium Iodide → [4-({2-[(2-Hydroxyethyl)oxy]ethyl}oxy)phenyl](4-hydroxyphenyl)methanone

Temperatur

80 °C

To a solution of 4,4′-dihydroxybenzophenone (3.0 g, 13.9 mmol) in DMF (30 mL) was added Cs2CO3 (13.55 g, 41.6 mmol). The mixture was heated at 80° C. under nitrogen for 1 h. The stirred reaction was cooled to room temperature and NaI (2.08 g, 13.9 mmol) was added, followed by dropwise addition of a solution of 2-(2-chloroethoxy) ethanol (1.63 mL, 15.3 mmol) in DMF (7 mL). The reaction mixture was heated at 80° C. under nitrogen overnight. The mixture was cooled to room temperature and quenched with saturated aqueous NH4Cl (100 mL), then extracted with EtOAc (3×60 mL). The organic layers were combined and washed with water, brine, and dried over Na2SO4, then concentrated to a light brown oil which was further purified by chromatography on a silica gel column eluted with a gradient from hexanes to 95% EtOAc:hexanes to give a light brown oil which contained some DMF. The residue was dissolved in EtOAc (100 mL) and further washed with water (2×50 mL), saturated aqueous CuSO4 (50 mL), water (50 mL) and brine (50 mL). The EtOAc solution was dried (Na2SO4) and concentrated to 15 mL and 30 mL of hexanes added. A white solid precipitated and was washed with 1:1 hexanes:EtOAc to afford compound 61 (1.90 g, 45%). mp 126-127° C. 1H NMR (400 MHz, CD3OD): δ 3.60-3.65 (m, 2H), 3.65-3.70 (m, 2H), 3.85-3.90 (m, 2H), 4.20-4.25 (m, 2H), 6.87 (d, J=8.6 Hz, 2H), 7.05 (d, J=8.8 Hz, 2H), 7.67 (d, J=8.6 Hz, 2H), 7.73 (d, J=8.8 Hz, 2H). LRMS (APCI): m/z, 303 (M+H)+, 301 (M−H)−.

1. customThe stirred reaction
2. temperaturewas cooled to room temperature
3. temperatureThe reaction mixture was heated at 80° C. under nitrogen overnight
4. temperatureThe mixture was cooled to room temperature
5. customquenched with saturated aqueous NH4Cl (100 mL)
6. extractionextracted with EtOAc (3×60 mL)
7. washwashed with water, brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated to a light brown oil which
10. customwas further purified by chromatography on a silica gel column
11. washeluted with a gradient from hexanes to 95% EtOAc
12. customhexanes to give a light brown oil which
13. washfurther washed with water (2×50 mL), saturated aqueous CuSO4 (50 mL), water (50 mL) and brine (50 mL)
14. dry with materialThe EtOAc solution was dried (Na2SO4)
15. concentrationconcentrated to 15 mL and 30 mL of hexanes
16. additionadded
17. customA white solid precipitated
18. washwas washed with 1:1 hexanes

ORD-Eintrag

ord-b1b4f18a23774c83a64bc1b8c0bb54ae

Quelldatensatz

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07560589B2