2-CHLORO-4-FLUORONICOTINIC ACID

Step A: 2-Chloro-4-i uoropyridine~3~carboxylic acid (64-2)A solution of LDA (97 ml, 1.8 M heptane/THF/ethylbenzene, 175 mmol) and THF (304 ml) were combined and cooled to -78°C. 2-Chloro-4-fluoropyridine (20.0 g, 152 mmol) was dissolved in 50 ml THF and then added dropwise over 20 minutes and then the solution was stirred for 1 hour. The reaction was poured onto dry ice and -the dry ice was allowed to evaporate. Water and 1 N NaOH were added to the residue. The mixture was extracted with EtTo a solution of Example 75a (2.74 g, 15.6 mmol) in THF (50 mL), tBuOCOCl ( 3.2 g, 23.4 mmol) at 0C was added TEA (3.16 g, 31.2 mmol), the mixture was stirred at r.t. for 0.5 min, and then NaBD4 ( 1.31 g, 31.2 mmol) in EtOH (10 mL) was added at 0C, which was turned to r.t for another 30 min. The reaction was then quenched by adding water (10 mL), then concentrated, the residue was purified by flash column chromatography (eluted with EtOAc) to give the desired product (Example 75b, 1.05 g, yield 41 %) as yellow oil. LCMS [M+1]+= 164To a solution of Example 74a (100 mg, 0.57 mmol) in THF (100 mL) was added BH3 (1M, 10 mL) in batch at 0Cand slowly warmed to 65C for 16h. After the reaction was completed, the solvent was removed under reduced pressure, and the residue was dissolved in EtOAc (50 mL), washed with aq. NH4C1 (20 mL*3), dried over Na2S04, filtered and concentrated to afford the desired product (Example 74b, 100 mg) as a yellow oil.Step 1: Ethyl 2-chloro-4-ethoxynicotinate (13). 5 A solution of

Molecular Weight:175.54
XLogP3:1.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:174.9836342
Monoisotopic Mass:174.9836342
Topological Polar Surface Area:50.2
Heavy Atom Count:11
Complexity:167
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes