反応 #469082

反応方程式

Magnesium

fluorobenzyl bromide

2-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone

pyridazinone

→

title compound

収率 28.0%

2-(2,2,2-Trifluoroethyl)-4-(4-fluorobenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone

収率 28.0%

溶媒

ether

THF

反応条件

後処理

1. 1
   その他All magnesium was consumed
2. 2
   その他resulting in a pale brownish-yellow solution
3. 3
   温度The mixture was heated for 3 hours
4. 4
   その他was consumed
5. 5
   温度) The reaction was cooled to room temperature
6. 6
   その他then quenched with a saturated NH4Cl solution
7. 7
   抽出The product was extracted with ethyl acetate (250 mL)
8. 8
   洗浄and the organic layer was washed with saturated NH4Cl, and brine
9. 9
   乾燥The ethyl acetate solution was dried over MgSO4
10. 10
    ろ過filtered
11. 11
    濃縮The filtrate was concentrated under reduced pressure
12. 12
    その他The product was isolated as an orange residue
13. 13
    その他Purification

実験手順

Magnesium turnings (500 mg) were placed in a dry 250 mL round bottom flask. Anhydrous ether (20 mL) was added under N2 at room temperature then fluorobenzyl bromide (3 mL) was added and stirred. The reaction was heated at 40° C. for 2 hours. All magnesium was consumed resulting in a pale brownish-yellow solution. The 2-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone prepared in Example 193E was dissolved in dry THF (25 mL) and transferred to the Grignard solution. The mixture was heated for 3 hours. TLC (2:1 hexanes/ethyl acetate) indicated that the pyridazinone starting material was consumed.) The reaction was cooled to room temperature then quenched with a saturated NH4Cl solution. The product was extracted with ethyl acetate (250 mL); and the organic layer was washed with saturated NH4Cl, and brine. The ethyl acetate solution was dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure. The product was isolated as an orange residue. Purification using a silica gel column (20:80 ethyl acetate/pentanes) provided the title compound as a pale yellow powder (yield: 140 mg, 28%). 1H NMR (300 MHz, CDCl3) δ 3.13 (s, 3H), 4.85 (m, 2H), 6.93 (m, 4H), 7.49 (d, J=9 Hz, 2H) 7.72 (s, 1H), 8.08 (d, J=9 Hz, 2H). MS (DCI/NH3) m/z 441 (M+H)+. Anal. calc. for C20H16F4N2O3S.0.5 H2O: C, 53.45; H, 3.81; N, 6.23. Found C, 53.45; H, 3.81; N, 6.23.

出典