Methyl 2-iodobenzoate

CLEAR YELLOW LIQUID

To a solution of 2-iodobenzoic acid (46) (15g/60mmol) in 200mL of methanol were added 8.8mL of sulfuric acid dropwise. The solution was refluxed for 16h. The mixture was allowed to cool to room temperature and most of the methanol was evaporated by rotary evaporator until approximately 20mL of solution. The product was then partitioned between water and dichloromethane. The aqueous phase was extracted 2×150mL of dichloromethane. The organic layer was then washed with 3×100mL of saturated solution of bicarbonate, 3×100mL of water, dried over sodium sulfate anhydrous, filtered and the organic solvent evaporated. Compound 47 was isolated as light yellow oil (15.4g/98percent).Methyl 2-iodobenzoate (47). IR νGeneral procedure: Iodobenzoic acid (10 g) was added to 60 mL of alcohol derivatives (methanol, ethanol, n-butanol, iso-butanol and sec-butanol) in 5 mL conc. H2-Iodobenzoic acid (7.50 g, 30.2 mmol, 1 equiv) was dissolved in MeOH (150 mL), then concentrated sulfuric acid (20 mL) was added slowly. The mixture was stirred and heated at reflux for 3 h. After cooling to r.t., the reaction mixture was diluted with Et2O (150 mL), the layers were separated, and the organic phase was washed with H2O (2 × 150 mL), sat. aq NaHCO3(200 mL) and sat. aq NaCl (200 mL). After drying over MgSO4, the solvent was removed in vacuo to give the product. Yield: 7.59 g (29.0 mmol, 96percent); colorless oil. 1H NMR (400 MHz, CDCl3): δ= 3.93 (s, 3 H), 7.14 (ddd, J= 8.0, 7.5, 1.7 Hz, 1 H), 7.39 (ddd, J= 7.7, 7.5, 1.2 Hz, 1 H), 7.79 (dd, J= 7.7, 1.7 Hz, 1 H), 7.99 (dd, J= 8.0, 1.2 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ= 52.5, 94.0, 127.9, 130.9, 132.6, 135.1, 141.3, 166.9. HRMS (EI): m/z [M – H]·+calcd for C8H6IO2: 260.9412; found:260.9407.General procedure: The carboxylic acid (0.271 mmol), TCT (0.050 g, 0.271 mmol), PS-Ph3P (0.009 g, 0.027 mmol, loading 3.0 mmol/g), and Na2CO3 (0.057 g, 0.542 mmol) were added to MeOH (0.5 mL). Then the mixture was sonicated in an ultrasonic bath (Elmasonic S 30H) at 50°C for the specified time. After completion, the crude mixture was filtered through a short pad of silica to obtain the product after solvent evaporation. Whenever necessary, the product was further purified by flash chromatography.To a stirred solution of 2-iodobenzoic acid (10.0 g, 40.32 mmol, 1 equiv) in MeOH (100 ml_) was added HGeneral procedure: The mixture of carboxylic acid, alcohol and N-bromosuccinimide was stirred in a 25 mL reactortube at 70 °C for 2–40 h. After the completion of the reaction, the mixture was cooled to roomtemperature and alcohol was evaporated under reduced pressure. The isolation procedure was as follows, except where noted differently in Section 3.2.6. The residue was dissolved in ethyl acetate andconsecutively washed with 10 mL of 10percent Na2S2O3 (aq), 5 mL of saturated NaHCO3 (aq) and 10 mL ofdistilled water. The water phase was extracted with ethyl acetate (3Χ5 mL). The organic layers were combined, dried over Na2SO4 and the solvent was evaporated under reduced pressure.General procedure: To a 15 mL test tube with septum Cs2CO3 (0.6 mmol, 195 mg), aromaticcarboxylic acid (1) (0.3 mmol), [Ir(dF(CF3)ppy)2dtbbpy]PF6 (D) (6 μmmol, 6.7 mg), NIS (1.5mmol, 337.5 mg) and I2 (60 μmol, 20 molpercent) were added. The tube was evacuated and backfilledwith argon for three times, and then 3 mL of dry DCE was added through a syringer under argon.The tube was sealed with Parafilm Mr® and placed in an oil bath with a contact thermometer, andthe reaction was carried out at 50 °C under irradiation with 6 × 5 W blue LEDs (λmax = 455 nm).After 24 h or 36 h, the resulting mixture was filtered through a 2 cm thick pad of silica, and thesilica was washed with DCM) (50 mL). The filtrate was collected and the solvent was removed invacuo. The crude residue was purified by silica gel flash column chromatography to provide thetarget product (2). (Note: The reaction was very sensitive to moisture, and the yields sharplydecreased to less than 5percent when 0.01 equivalent of H2O was added to the reaction system).General procedure: Under Ar atmosphere in a dry Schlenk tube, a mixture of NaH (6.0 mmol) and trifluoroacetate (6.0 mmol) was stirred in THF (5 mL) at room temperature for 10 min. To this mixture enolizable ketones (5.0 mmol) in THF (5 mL) was added dropwise at 0 °C under Ar atmosphere. After stirring for 2–6 h at reaction temperature, the reaction solution was cooled to 0 °C again and quenched with 6 mL of 1 mol/L HCl. After stirring for additional 15 min, the mixture was neutralized with saturated NaHCO3 solution. After usual workup, the residue was purified by chromatography on silica gel to afford the trifluoromethyl alkyl ketone products.#10;

Molecular Weight:262.04
XLogP3:2.7
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:261.94908
Monoisotopic Mass:261.94908
Topological Polar Surface Area:26.3
Heavy Atom Count:11
Complexity:147
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes