Reaction #501823

Reaction equation

propargylmagnesium bromide

2-chloro-4'-fluoroacetophenone

diethyl ether

diethyl ether

→

4,5-epoxy-4-(4'-fluorophenyl)-1-pentyne

Yield 79.0%

Conditions

Workup

1. 1
   Otherquenched with 50 mL of saturated NH4Cl
2. 2
   OtherThe layers were separated
3. 3
   Extractionthe aqueous phase extracted twice with 100 mL diethyl ether
4. 4
   DryingThe combined ether extracts were dried (MgSO4)
5. 5
   Otherthe solvent removed at reduced pressure
6. 6
   workup.DISSOLUTIONThis residue was dissolved in 250 mL of dry diethyl ether
7. 7
   workup.ADDITIONadded to 4.9 g of pulverized NaOH
8. 8
   workup.STIRRINGThis mixture was stirred at 24° C. for 3.5 hours
9. 9
   workup.ADDITION0.5 g of NaOH was added
10. 10
    workup.WAITAfter an additional 2.5 hours
11. 11
    workup.ADDITIONthe mixture was poured into 100 mL of H2O
12. 12
    Extractionextracted with diethyl ether
13. 13
    OtherThe ether layer was separated
14. 14
    Dryingdried (MgSO4)
15. 15
    Concentrationconcentrated under reduced pressure
16. 16
    workup.DISTILLATIONDistillation under reduced pressure (94°-95° C. at 0.65 mmHg)

Procedure

To a solution of 23.1 g (0.16 mol) of propargylmagnesium bromide (J. Am. Chem. Soc., 83, 1686, 1961) in 50 mL of dry diethyl ether at 25° C. was added 20.0 g (0.115 mol) of 2-chloro-4'-fluoroacetophenone in 150 mL of diethyl ether over a 0.25 hour period. The solution was stirred at 25° C. for 15 hours and then quenched with 50 mL of saturated NH4Cl. The layers were separated and the aqueous phase extracted twice with 100 mL diethyl ether. The combined ether extracts were dried (MgSO4) and the solvent removed at reduced pressure. This residue was dissolved in 250 mL of dry diethyl ether and added to 4.9 g of pulverized NaOH. This mixture was stirred at 24° C. for 3.5 hours and then 0.5 g of NaOH was added. After an additional 2.5 hours, the mixture was poured into 100 mL of H2O and extracted with diethyl ether. The ether layer was separated, dried (MgSO4) and concentrated under reduced pressure. Distillation under reduced pressure (94°-95° C. at 0.65 mmHg) yielded 16 g (79%) of 4,5-epoxy-4-(4'-fluorophenyl)-1-pentyne as an oil, homogeneous by TLC and spectroscopic criteria; Rf 0.75 (1:1 hexanes-diethyl ether): IR (film) 3290, 1600, 1505, 1225 cm-1 ; 1HNMR (300 MHz, CDCl3) δ 7.5-7.4 (m, 2H), 7.1-7.05 (m, 2H, 3.02 (ABq, 2H, JAB =6.0 Hz, ΔνAB =119.8 Hz), 2.92 (t, 2H, J=2 Hz), 2.07 (t, 1H, J=2 Hz).

Source