2-(Trifluoromethyl)pyridine

General procedure: To a well stirred mixture of AgF (1.27 g, 10 mmol) in 10 ml of DMF, Me2-bromopyridine (1.58 g, 0.01 mol) was added to a 100 ml three-necked flask under N2 protection.25 ml of DMF, Cu powder (1.92 g, 0.03 mol), stirring was started, and the ice water bath was cooled to 0-5 °C. add Umemoto reagent (8.76g, 0.02mol).After stirring for 1 h in an ice water bath, the mixture was further heated to 80 ° C for 3 h.The reaction solution was subjected to 19F NMR analysis using OTf as an internal standard, and the yield was 96percent.General procedure: To the suspension of zinc powder (without activation, 65.4 mg, 1.0 mmol, Aldrich 99.995percent purity) in DMPU (0.5 mL), trifluoromethyl iodide (ca. 2.5 mmol, sufficiently dissolved in the solution) was added at room temperature under argon atmosphere. After the solution was stirred for 2 h at room temperature, CuI (1.9 mg, 0.01 mmol, 2 mol percent), 1.10-phenanthroline (1.8 mg, 0.01 mmol, 2 mol percent), and then aryl iodide 1a (138.0 mg, 0.5 mmol) were added. The reaction mixture was stirred at 50 °C for 24 h. After cooling to room temperature, the yield of product 2a was determined by A 2.5M solution of BuLi in hexane (13.6 mL) was diluted in THF (50 mL) and cooled to -78C (dry ice/acetone). To this solution were subsequently added 2, 2, 6, 6-tetramethylrhoirhoeridine (4.8 g) and commercially available 2-(trifluoiOmethyl)pyridine (5 g). The mixture was stirred at -780C for 2 h and then a solution of iodine (17.3 g) in THF (50 mL) was added. The cooling bath was removed and the mixture was stirred at room temperature overnight. Then the mixture was quenched with IM aqueous Na2S2O3 (50 mL), the organic phase was separated and the aqueous phase was extracted with EtOAc. The combined organic phases were dried (MgSO4), filtered, concentrated and purified by chromatography (silica, CH2Cl2) to afford the title compound as a pale yellow solid (6.3 g, 68%). 1H-NMR (CDCl3) D= 8.63 (dd, 1 H), 8.36 (d, 1 H), 7.20 (dd, 1 H).Diethyl ether (4.32 L) and hexanes (5.40 L) were added to the reaction vessel under N2 atmosphere, and cooled to -75 C. to -65 C. Dropwise addition of n-Butyl lithium (3.78 L in 1.6 M hexane) under N2 atmosphere at below -65 C. was followed by dropwise addition of dimethyl amino ethanol (327.45 g, 3.67 mol) and after 10 min. dropwise addition of Example 2, Step 1: Preparation of 6-trifluoromethyl-pyridine-2-carboxylic acid Diethyl ether (4.32 L) and hexanes (5.40 L) were added to the reaction vessel under N2 atmosphere, and cooled to -75 C. to -65 C. Dropwise addition of n-Butyl lithium (3.78 L in 1.6 M hexane) under N2 atmosphere at below -65 C. was followed by dropwise addition of dimethyl amino ethanol (327.45 g, 3.67 mol) and after 10 min. dropwise addition of General procedure: In a test tube equipped with a stirring bar and a septum rubber, Under argon flow, bis (trifluoromethyl) zinc (DMPU) 2 complex (92 mg, 0.2 mmol), After adding copper (I) chloride (1.9 mg, 0.01 mmol), DMPU (0.2 ml) and ethyl 2-iodobenzoate (0.1 mmol, 16.6 mul)Replace septum rubber with screw cap, The reaction was carried out at 50 C. for 24 hours.After completion of the reaction, After cooling, As a result of quantification by 19 F-NMR using benzotrifluoride using the reaction solution as an internal standard substance, The yield of the objective ethyl 2- (trifluoromethyl) benzoate was 82%.General procedure: In a 10-15 mL vial with a magnetic stirrer, copper (I) chloride (0.3 g, 3.0 mmol, 1 eq) was added and the vial was sealed in the glove box under argon. To this vial, under argon 3 mL of dry DMF was added and the resulting reaction mixture was stirred at room temperature for 5 minutes. To this reaction mixture a solution of t-BuOK in DMF (0.68 g, 6.06 mmol, 2 eq) was added drop wise and the resulting reaction mixture was stirred at room temperature for 5 minutes. After 5 minutes, CF3H was bubbled into this THF solution for 4 min 11 sec (0.636 g, 9.09 mmol was added total at the rate of 52.5 ml/min, 3 eq) and the resulting reaction mixture was stirred at room temperature for 10 minutes. After 10 minutes, a solution of triethylamine trihydrofluoride (TREAT HF) (0.195 g, 1.21 mmol, 198 mum) was added to the reaction mixture neat. To the same reaction mixture iodobenzene (0.927 g, 4.54 mmol, 1.5 eq) was added neat and the resulting reaction mixture was heated at 50 C. for 24 hours. The reaction mixture was cooled to room temperature and then hexafluorobenzene (C6F6) (0.166 eq) was added to the reaction mixture and it was stirred at room temperature for 10 mins. An aliquot of reaction mixture was taken out and its NMR (19F) was recorded. NMR yields were determined by NMR integrations and are reported in Table 5.

Molecular Weight:147.10
XLogP3:1.8
Hydrogen Bond Acceptor Count:4
Exact Mass:147.02958362
Monoisotopic Mass:147.02958362
Topological Polar Surface Area:12.9
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes