Reaktion #47952

Reaktionsgleichung

thionyl chloride

ethylmagnesium bromide

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

triethylamine

→

4-ethyl-6-chloro-4-phenyl-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITAfter an additional 30 min at 0° C.
2. 2
   Sonstigethe reaction was quenched
3. 3
   workup.ADDITIONby pouring into a well
4. 4
   workup.ADDITIONmixture of 300 mL EtOAc and 200 mL water which
5. 5
   workup.ADDITIONThe layers were mixed
6. 6
   Sonstigeseparated
7. 7
   Waschenthe organic layer washed with 200 mL brine
8. 8
   Filtrationfiltered
9. 9
   Sonstigeto remove unreacted
10. 10
    EinengenThe filtrate was concentrated in vacuo
11. 11
    SonstigePurification by normal phase chromatography (120 g silica gel cartridge, 10-75% EtOAc/hexanes)

Vorschrift

To a −20° C. solution of 6-chloro-4-hydroxy-4-phenyl-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one (5.5 g, 15 mmol) in THF (50 mL) was added triethylamine (10.7 mL, 77 mmol) and then thionyl chloride (1.2 mL, 17 mmol) was added dropwise. After 20 min, 1M ethylmagnesium bromide in THF (46 mL, 46 mmol) was added over 10 min. and the reaction mixture warmed to 0° C. After an additional 30 min at 0° C., the reaction was quenched by pouring into a well stirred mixture of 300 mL EtOAc and 200 mL water which was acidified with 1N HCl solution. The layers were mixed and separated and the organic layer washed with 200 mL brine and filtered to remove unreacted starting material. The filtrate was concentrated in vacuo. Purification by normal phase chromatography (120 g silica gel cartridge, 10-75% EtOAc/hexanes) provided 4-ethyl-6-chloro-4-phenyl-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one. 1H NMR (CDCl3, 400 MHz) δ 8.73 (s, NH); 7.39 (m, 3H); 7.35 (m, 2H); 7.09 (dd, 1H, J=8.43 and 2.2 Hz); 6.70 (d, 1H, J=8.43 Hz); 6.49 (d, 1H, J=2.38 Hz); 3.92 (dq, 1H, J=9.52 and 15.9 Hz); 3.47 (dq, 1H, J=8.61 and 17 Hz); 2.41 (dq, 1H, J=7.14 and 14.29 Hz); 2.28 (dq, 1H, J=7.14 and 14.28 Hz); 0.91 (t, J=7.14 Hz, 3H); MS (Electrospray): m/z 369.2 (M+H)

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