Yield:60064-34-8 64%

Reaction Conditions:

Stage #1: ethanol;2-Amino-4-chlorobenzoic acid;sulfuric acid for 72 h;Reflux;
Stage #2: with sodium hydrogencarbonate in ethanol;water;

Steps:

6; I

Procedure I: Acid-catalyzed esterification (Exemplified by 31a)l-amino-4-chloro-benzoic acid (500 mg, 2.9 mmol) and H₂S0₄ (cone, 0.5 mL) in EtOH (30 mL) was refluxed for 3 days before being concentrated to half- volume and diluted with NaHC03 (aq, sat) and extracted with DCM (3x) (even though the reaction had not yet finished). The pooled DCM fractions was washed with brine, dried over MgS0₄, concentrated and purified by column chromatography (toluene: acetone 100:0 -> 98:2) to give the ethyl ester in 64%> yield (370 mg).; 2-[2-(2-fluorobenzoylamino)-benzoylamino]-4-chlorobenzoic acid - Compound 35a35b was synthesized by procedures I, A, J, A, and C.

References:

WO2011/155898,2011,A1 Location in patent:Page/Page column 52; 57