Benzoic acid, 3-chloro-4-fluoro-, methyl ester

off-white powder

Preparation of methyl 3-chloro-4-fluoro-benzoate In a 250 ml four-necked round bottom flask, equipped with a mechanical stirrer, condenser and thermometer, 86.5 g of 3-chloro-4-fluoro-benzoic acid chloride are loaded and 28.1 g of anhydrous MeOH are added by a dosing funnel. The reaction is exothermic and spontaneously reaches 60°C. The methanol is metered keeping the temperature at about 60°. It is stirred for 1 hour then the excess methanol is distilled. In this way 80 g of yellow oil are obtained corresponding to the compound methyl 3-chloro-4-fluoro-benzoate. Yield 97.29percent.A round bottomed flask was charged with 3-chloro-4-fluoro-benzoic acid (2.0 g, 11.4 mmol), sulfuric acid (0.33 g, 3.4 mmol), MeOH (20 mL) and refluxed for 16 h (TLC indicatedcomplete consumption of starting material). The volatiles were removed under reducedpressure; the residue was diluted with water (15 mL) and extracted with EtOAc (3 x 50 mL).The combined organic extracts were washed with brine (50 mL), dried over Na2S04 andconcentrated in vacuo to give the crude residue which was purified by columnchromatography (100-200 silica gel, 40 g, 10percent EtOAc-hexane) to afford methyl3-chloro-4-fluoro-benzoate ( 1.5 g, 69percent) as a light yellow oil. 1H NMR [300 MHz, CDCh]: J 8.08 (dd, J = 6.9, 2.1 Hz, 1H), 7.94-7.89 (m, 1H), 7.18 (t, J =8.7 Hz, 1H), 3.90 (s, 3H).Preparative Example 29.; A round bottomed flask was charged with 3-chloro-4-fluorobenzoic acid (5.0 g, 28.6 mmol), sulfuric acid (0.84 g, 8.6 mmol), and methanol (60 mL). The solution was heated at reflux overnight. The methanol was removed in vacuo. The residue was extracted with ethyl acetate (5 x), dried over sodium sulfate, filtered and concentrated in vacuo to yield 4.73 g (88percent).A round bottomed flask was charged with the ester intermediate (4.73 g, 25 mmol), potassium carbonate (3.45 g, 25 mmol), piperazine-1-carboxylic acid tert-butyl ester (5.59 g, 30 mmol) and acetonitrile (6 mL). The mixture was heated at 65

Molecular Weight:188.58
XLogP3:2.6
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:188.0040353
Monoisotopic Mass:188.0040353
Topological Polar Surface Area:26.3
Heavy Atom Count:12
Complexity:174
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes