Reaction #57948

Reaction equation

2-(3,5-bis-trifluoromethyl-benzoylamino)-4-hydroxy-benzoic acid methyl ester

1,3-dibromopropane

potassium carbonate

→

2-(3,5-bis-trifluoromethyl-benzoylamino)-4-(3-bromo-propoxy)-benzoic acid methyl ester

Yield 78.0%

Solvents

acetone

Conditions

Workup

1. 1
   TemperatureThe reaction mixture was heated
2. 2
   Temperatureto reflux for 3 hours
3. 3
   OtherThe mixture was partitioned between ethyl acetate and brine
4. 4
   Otherthe layers were separated
5. 5
   ExtractionThe aqueous layer was extracted with one additional portion of ethyl acetate
6. 6
   Washwashed with one portion of brine
7. 7
   Dryingdried over anhydrous magnesium sulfate
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated under reduced pressure
10. 10
    OtherThe crude oil was purified by flash chromatography through silica gel

Procedure

To a solution of 2-(3,5-bis-trifluoromethyl-benzoylamino)-4-hydroxy-benzoic acid methyl ester (10.10 g, 2.70 mmol) and 1,3-dibromopropane (2.18 g, 10.8 mmol) in acetone (75 mL) was added potassium carbonate (1.87 g, 13.5 mmol). The reaction mixture was heated to reflux for 3 hours and allowed to cool back down to room temperature. The mixture was partitioned between ethyl acetate and brine, and the layers were separated. The aqueous layer was extracted with one additional portion of ethyl acetate. The organics were combined, washed with one portion of brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude oil was purified by flash chromatography through silica gel using ethyl acetate/hexanes (0/100 gradient to 8/92) to give 2-(3,5-bis-trifluoromethyl-benzoylamino)-4-(3-bromo-propoxy)-benzoic acid methyl ester (1.11 g, 78%) as a white powder. 1H NMR (400 MHz, CDCl3); δ 12.58 (s, 1H), 8.53 (d, 1H), 8.51 (s, 2H), 8.08 (s, 1H), 8.04 (d, 1H), 6.70 (dd, 1H), 4.24 (t, 2H), 3.96 (s, 3H), 3.62 (t, 2H), 2.37 (m, 2H).

Source