Reaktion #47975

Reaktionsgleichung

thionyl chloride

cyclopropylmagnesium bromide

6-chloro-4-(4-bromophenyl)-4-hydroxy-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one

triethylamine

→

6-chloro-4-cyclopropyl-4-(4-bromophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITAfter 10 min
2. 2
   TemperaturThe reaction mixture was warmed from −18° C. to 0° C.
3. 3
   workup.STIRRINGto stir for 6 hours
4. 4
   Sonstigequenched with 25 mL 1N aqueous HCl
5. 5
   Extraktionextracted with 150 mL ethyl acetate
6. 6
   WaschenThe organic layer was washed with brine (100 mL)
7. 7
   Trocknendried over MgSO4
8. 8
   Filtrationfiltered
9. 9
   Einengenconcentrated in vacuo
10. 10
    SonstigePurification by normal phase chromatography (120 g silica gel cartridge, linear gradient 10-70% EtOAc/hexanes)
11. 11
    Sonstigefollowed by crystallization from hexanes

Vorschrift

To a −18° C. solution of 6-chloro-4-(4-bromophenyl)-4-hydroxy-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one (2 g, 4.6 mmol) in anhydrous THF (20 mL) was added triethylamine (2.6 mL, 18 mmol). The reaction was stirred for 5 min and then thionyl chloride (0.0.37 mL, 5 mmol) was added dropwise. After 10 min, 0.5M cyclopropylmagnesium bromide in THF (36 mL, 18 mmol) was added. The reaction mixture was warmed from −18° C. to 0° C. and allowed to stir for 6 hours and then quenched with 25 mL 1N aqueous HCl and extracted with 150 mL ethyl acetate. The organic layer was washed with brine (100 mL), dried over MgSO4, filtered, and concentrated in vacuo. Purification by normal phase chromatography (120 g silica gel cartridge, linear gradient 10-70% EtOAc/hexanes) followed by crystallization from hexanes gave 6-chloro-4-cyclopropyl-4-(4-bromophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one as a green solid. 1H NMR (CDCl3, 400 MHz) δ 7.56 (s, NH); 7.46 (br d, 2H, J=8.61 Hz); 7.21 (dd, 1H, J=8.42 and 2.20 Hz); 7.12 (br d, 2H, J=7.14 Hz); 6.85 (br m, 1H); 6.68 (d, 1H, J=8.24 Hz); 4.27 (m, 2H); 1.6 (obs, 1H); 0.77 (m, 2H); 0.19 (m, 1H); 0.09 (m, 1H); MS (Electrospray): m/z 459.0 (M+H, Br=79).

Quelle