Reaction #469082

Reaction equation

Magnesium

fluorobenzyl bromide

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

pyridazinone

→

title compound

Yield 28.0%

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

Yield 28.0%

Solvents

ether

THF

Conditions

Workup

1. 1
   OtherAll magnesium was consumed
2. 2
   Otherresulting in a pale brownish-yellow solution
3. 3
   TemperatureThe mixture was heated for 3 hours
4. 4
   Otherwas consumed
5. 5
   Temperature) The reaction was cooled to room temperature
6. 6
   Otherthen quenched with a saturated NH4Cl solution
7. 7
   ExtractionThe product was extracted with ethyl acetate (250 mL)
8. 8
   Washand the organic layer was washed with saturated NH4Cl, and brine
9. 9
   DryingThe ethyl acetate solution was dried over MgSO4
10. 10
    Filtrationfiltered
11. 11
    ConcentrationThe filtrate was concentrated under reduced pressure
12. 12
    OtherThe product was isolated as an orange residue
13. 13
    OtherPurification

Procedure

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.

Source