4-FLUORO-3-NITROBENZYLALCOHOL96

Sodium borohydride (2.70 g, 64.83 mmol)Dissolved in 100mL of tetrahydrofuran, Cool to 0 ° C, 4-Fluoro-3-nitrobenzoic acid 5a (12.0 g, 64.83 mmol) was added portionwise0 ° C for 1 hour.Then at 0 ° CAdd boron trifluoride diethyl ether solution dropwise(6.55 mL, 71.31 mmol), The reaction was warmed to room temperature for 3 hours.The reaction mixture was added with 500 mL of ethyl acetate and 300 mL of water, the layers were separated, the organic phase was washed with saturated sodium chloride solution (500 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to give 4- Nitrobenzyl alcohol 5b (11.0 g, pale yellow solid), yield: 99.1percent.Sodium borohydride (2.70 g, 64 . 83 mmol) dissolved in 100 ml in tetrahydrofuran, cooled to 0 °C, batch by adding 4 - fluoro -3 - nitro benzoic acid 4a (12.0 g, 64 . 83 mmol), 0 °C reaction 1 hours. Then in 0 °C [...] boron trifluoride ethyl ether solution under (6.55 ml, 71 . 31 mmol), the reaction temperature to room temperature the reaction solution 3 hours. To the reaction solution by adding 500 ml ethyl acetate and 300 ml water, layered, organic phase using saturated sodium chloride solution (500 ml) washing, drying with anhydrous sodium sulfate, filtered, the filtrate is concentrated under reduced pressure, to obtain 4-fluoro-3-nitrobenzyl alcohol is yellow 4b (11.0 g, yellow solid), yield: 99.1percent.Synthesis of dimethylcarbamic acid 2-oxo-2H-3-(4-fluoro-3-(piperidinylethyl) aminosulfonylbenzyl)-4-methyl-6-chloro- l -benzopyran-7-yl ester (subject compound 13)Subject compound 13 is synthesized following the procedure described in Scheme 2. 4-Fluoro-3-nitrobenzyl alcohol (2):Sodium borohydride (22.6 g, 590 mmol) is dissolved in 700ml of tetrahydrofuran, and is cooled to 0°C with an ice-salt bath. To this solution is added portion-wise 4-fluoro-3-nitrobenzoic acid (100 g, 540 mmol, subject compound 1) at 0°C, and the resulted solution is stirred at 0°C for 1 h. To the solution is then added dropwise a tetrahydrofuran solution of boron trifluoride-dimethyl ether (54.2 mL, 590 mmol) at 0°C. After adding, the reaction is continued at room temperature for 3 h. After the reaction is completed as indicated by TLC, the reaction is quenched with ice water, extracted with ethyl acetate, washed with saturated saline, and dried over anhydrous sodium sulfate. The solvent is removed to give a white solid (subject compound 2, 90 g, 97.4percent).To a solution of Intermediate 46(1.00 g, 5.40 mmol) in THF (10 mL) was added asuspension of NaBH4 (0.24 g, 5.94 mmol) in THF (10 mL) at 0°C. The reaction mixturewas stirred at room temperature for 1 h. Boron trifluoride diethyl etherate (0.84 g, 5.94 mmol) was added at 0°C. The reaction mixture was stirred at room temperature for 16 h, then quenched with brine (100 mL) and extracted with EtOAc (2 x 100 mL). The organic layer was separated, washed with H20 (100 mL) and brine (100 mL), then dried overanhydrous Na2SO4 and concentrated in vacuo. The crude residue was purified by column chromatography (silica, 100-200 mesh, 50percent EtOAc in hexanes) to afford the title compound (0.80 g, 87percent) as a colourless liquid. oH (400 MHz, CDC13) 4.78 (d, J3.34 Hz, 2H), 7.24-7.34 (m, 1H), 7.61-7.71 (m, 1H), 8.09 (d, J6.68 Hz, 1H) (OH signal absent).Compound 2c-2: 4-Fluoro-3-nitrobenzyl alcohol; [Show Image] Sodium borohydride (1.36 g, 35.95 mmol) was added to a solution of 4-fluoro-3-nitrobenzaldehyde (2.0 g, 11.83 mmol) in methanol (15 mL) and water (3.0 mL), and the mixture was stirred at room temperature for 3 hours. Water was then added to the reaction mixture, and extraction was performed with ethyl acetate. The organic extract was washed with saturated saline and dried over magnesium sulfate, and then concentrated under reduced pressure to yield the title compound (2.10 g, 95percent) as a pale red oil. 4-Fluoro-3-nitrobenzyl alcohol Sodium borohydride (1.36 g, 35.95 mmol) was added to a solution of 4-fluoro-3-nitrobenzaldehyde(2.0 g, 11.83 mmol) in methanol (15 mL) and water (3.0 mL), and the mixture was stirred at room temperature for 3 hours. Water was then added tothe reaction mixture, and extraction was performed with ethyl acetate. The organic extract was washed with saturated saline and dried over magnesiumsulfate, and then concentrated under reduced pressure to yield the titlecompound (2.10 g, 95percent) as a pale red oil

Molecular Weight:171.13
XLogP3:1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:171.03317122
Monoisotopic Mass:171.03317122
Topological Polar Surface Area:66
Heavy Atom Count:12
Complexity:171
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes