Reaction #4556

Reaction equation

phenol

HCl

bromide

carbonate

4-(4-chloro-2-fluorophenoxy)phenol

ethyl 4-bromopentanoate

potassium carbonate

→

ester

Ethyl 4-(4-(4-Chloro-2-fluorophenoxy)phenoxy)pentanoate

Solvents

DMF

Conditions

Workup

1. 1
   Otherhad reacted
2. 2
   TemperatureAfter cooling
3. 3
   Extractionthe product extracted into a 1:1 mixture of ether-pentane (2×150 ml)
4. 4
   Washwashed with 10% NaOH solution (200 ml)
5. 5
   Dryingdried (MgSO4)
6. 6
   Otherthe solvent evaporated
7. 7
   OtherThe resulting orange oil was purified via preparative HPLC (9:1 hexane/ethyl acetate) with the second peak
8. 8
   Otherbeing collected
9. 9
   OtherRemoval of the solvent

Procedure

A stirred mixture of 4-(4-chloro-2-fluorophenoxy)phenol (2.3 g, 0.0103 mol), ethyl 4-bromopentanoate (2.01 g, 0.0103 mol), and potassium carbonate (1.46 g, 0.105 mol) in DMF (20 ml) was heated in an oil bath at 130° C. for one hour. Additional bromide (0.5 g) and carbonate (0.5 g) were added each hour for the next four hours. At the end of this period, gas chromatography indicated that most of the starting phenol had reacted. After cooling, the reaction mixture was poured into 4N HCl solution (200 ml), and the product extracted into a 1:1 mixture of ether-pentane (2×150 ml). The organic extracts were combined, washed with 10% NaOH solution (200 ml), dried (MgSO4), then the solvent evaporated. The resulting orange oil was purified via preparative HPLC (9:1 hexane/ethyl acetate) with the second peak being collected. Removal of the solvent gave the desired ester as a light yellow oil: RI=1.5344 @ 25° C. Calc: C, 62.21; H, 5.50. Found: C, 62.38; H, 5.33.

Source