(3-FLUORO-PHENOXY)-ACETICACID

General procedure: An appropriately substituted phenol (50 mmol) was added to a solution of NaOH (187.5 mmol) in 15 mL of H2O. Chloroacetic acid (85 mmol) was added slowly at to the resulting solution at 40 C and the reaction mixture was heated to 85 C. Stirring was continued for 2 h, the reaction was cooled to room temperature and 100 mL H2O was added. The reaction was filtered and the filtrate was acidified with concentrated HCl to pH 1-2. The brown oil fraction which formed was extracted to diethylether (2 × 50 ml). The ether fraction, in turn, was extracted with an aqueous solution of 5% Na2CO3 (2 × 37.5 ml). The combined Na2CO3 fractions were acidified to pH 1-2 with concentrated HCl and the resulting precipitate was collected by filtration and oven dried to obtain the required acids.24To a mixture of General procedure: To a round bottom flaskwas added 1 (1.41 g, 4.5 mmol), (3-methyl-phenoxy)acetic acid (3.0 g, 18.1 mmol), and DMAP (550 mg, 4.5 mmol) in DCM (30 ml) at ambienttemperature. Once a homogenous solution was observed, DIC wasadded (2.8 ml, 18.1 mmol). The mixture was allowed to stir overnight.The next morning the mixture was filtered, and the filtrate was rotovapedonto silica gel and subjected to flash chromatography. The resultantfoam was then crystallized from methanol and DCM yielding1.08 g of white crystal (73%).General procedure: For the remaining eleven para-substituted carboxy-containinganalogs of GRI392104 (Table 1), the same reagents were combinedin a clean, dry flask in 1 mL dimethyl sulfoxide (DMSO). After 5 minof stirring, the clear solution turned amber and 140 lmol of solidpara-carboxy amine building block was dissolved into the reactionmixture. Over the course of an hour, the amber solution slowly turned cloudy white. The reactions were worked up in the samemanner as the other twenty-two carboxy analogs, except ethylacetate was used instead of methylene chloride before synthesiswas confirmed with 1H NMR. Products were then purified over10 g Biotage SNAP columns at 25 mL/min (method C) or via preparativeTLC in 92.5:7.5 chloroform/methanol (method D). Productsfrom method D were extracted in 50:50 ethyl acetate/methylenechloride and dried to a solid white residue. Purity was confirmedvia 1H NMR before drying the products to a solid white powder(Supplemental Fig. 1). 13C NMR data was collected for all previouslyunreported compounds (Supplemental Fig. 2). High resolution MSdata for all previously unreported compounds gave the expectedmass values with absolute errors ranging from 0.0 to 20.3 ppm.Compounds were stored at 3 mM in DMSO for activity analysis.

Molecular Weight:170.14
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:170.03792224
Monoisotopic Mass:170.03792224
Topological Polar Surface Area:46.5
Heavy Atom Count:12
Complexity:160
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes