Reaction #57949

Reaction equation

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

4-tert-butyl-benzaldehyde oxime

cesium carbonate

→

2-{[3,5-bis(trifluoromethyl)benzoyl]amino}-4-[3-({[(1E)-(4-tert-butylphenyl)methylidene]amino}oxy)propoxy]benzoic acid methyl ester

Yield 48.0%

Solvents

acetone

Conditions

Workup

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

Procedure

To a solution of 2-(3,5-bis-trifluoromethyl-benzoylamino)-4-(3-bromo-propoxy)-benzoic acid methyl ester (0.53 g, 1.00 mmol) and 4-tert-butyl-benzaldehyde oxime (0.20 g, 1.10 mmol) in acetone (35 mL) was added cesium carbonate (1.30 g, 4.00 mmol). The mixture was heated to reflux overnight and then allowed to cool back to room temperature. The mixture was partitioned between ethyl acetate and brine and the layers were then separated. The aqueous layer was extracted with two additional portions of ethyl acetate. The organics were combined, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude oil was purified by flash chromatography through silica gel using diethyl ether/hexanes (0/100 gradient to 5/95) to give 2-{[3,5-bis(trifluoromethyl)benzoyl]amino}-4-[3-({[(1E)-(4-tert-butylphenyl)methylidene]amino}oxy)propoxy]benzoic acid methyl ester (0.30 g, 48%) as an off-white solid. 1H NMR (400 MHz, CDCl3); δ 12.52 (s, 1H), 8.51 (d, 1H), 8.48 (s, 2H), 8.06 (s, 1H), 8.04 (s, 1H), 7.99 (d, 1H), 7.47-7.35 (AA′BB′, 4H), 6.67 (dd, 1H), 4.34 (t, 2H), 4.22 (t, 2H), 3.92 (s, 3H), 2.23 (m, 2H), 1.28 (s, 9H).

Source