(3-Bromo-5-fluorophenyl)methanol

(3-Bromo-5-fluorophenyl)methanol. 3-Bromo-5-fluorobenzoic acid (1.0 g, 4.52 mmol) was suspended in tetrahydrofuran (8 mL) and cooled to 0° C. To this solution was added borane tetrahydrofuran complex (1 M in tetrahydrofuran, 9 mL, 9.0 mmol) cautiously over 15 min. The reaction mixture was allowed to warm to room temperature overnight. The mixture was cooled to 0° C., treated with excess methanol, diluted with ethyl acetate, washed with 1 N sodium hydroxide (2.x.), then brine (2.x.), dried over sodium sulfate, and concentrated to afford 0.88 g (95percent) as a white powder. To a solution of 3-bromo-5-fluorobenzoic acid (4.38 g, 20.0 mmol) Of tetrahydrofuran(20 mL)A solution of 1M borane tetrahydrofuran complex in tetrahydrofuran (30 mL, 30. Ommol).Continue stirring at 0 ° C for 1.5 hours, Then stirred at room temperature overnight. Methanol was slowly added to it at room temperature until no gas had escaped to quench. The solvent was evaporated under reduced pressureThe crude product was purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 10/1), A pale yellow liquid (3.9 g, 95percent)[00127] A solution of 3-bromo-5-fluorobenzoic acid (2.74 g, 12.5 mmol) in tetrahydrofuran (6 mL), at 0°C under nitrogen, was treated with borane-tetrahydrofuran complex (1M, 15 mL, 15 mmol) in small portions over 12 mm, and the reaction was then stirred at 0°C for 70 minutes, and at room temperature for 22 h. The reaction was quenched by addition of methanol (10 mL), and the methanolic mixture was stirred at room temperature for 3 h, and then evaporated in vacuo, with co-evaporation from methanol, then from ethyl acetate, to give the crude product. The material was dissolved in ethyl acetate (200 mL), and the solution was washed with 0.5M aqueous sodium hydroxide (200 mL), and with saturated aqueous sodium chloride (100 mL); then dried over sodium sulfate; filtered and evaporated in vacuo to give 3-bromo-5-fluorobenzyl alcohol (1.79 g, 67percent). 1H NMR (400 MHz, CDCI3): ö 7.29 (s, IH), 7.15 (ddd, JHF = 8.2 Hz, JHH = 2.2, 1.8 Hz, 1H), 7.00-7.02 and 7.02-7.04 (dm, JHF = 9.2 Hz, JHH = unresolved, 1H), 4.66 (s, 2H), 2.04 (br s, 1 H); 19F NMR (377 MHz, CDCI3): -111.05 (dd, JHF = 9.3, 8.0 Hz, 1 F); 13C NMR (101 MHz, CDCI3):162.87 (d, JCF 250.6 Hz), 145.42 (d, JCF = 6.9 Hz), 125.45 (d, JCF = 3.1 Hz), 122.69 (d, JCF = 9.2 Hz), 118.01 (d, JCF = 24.6 Hz), 112.51 (d, JCF = 21.5 Hz), 63.60 (d, JCF = 2.3 Hz).A solution of 3-bromo-5-fluorobenzoic acid (2.74 g, 12.5 mmol) in tetrahydrofuran (6 mL), at 0°C under nitrogen, was treated with borane-tetrahydrofuran complex (1 M, 15 mL, 15 mmol) in small portions over 12 min, and the reaction was then stirred at 0°C for 70 minutes, and at room temperature for 22 h. The reaction was quenched by addition of methanol (10 mL), and the methanolic mixture was stirred at room temperature for 3 h, and then evaporated in vacuo, with co-evaporation from methanol, then from ethyl acetate, to give the crude product. The material was dissolved in ethyl acetate (200 mL), and the solution was washed with 0.5M aqueous sodium hydroxide (200 mL), and with saturated aqueous sodium chloride (100 mL); then dried over sodium sulfate; filtered and evaporated in vacuo to give 3-bromo-5- fluorobenzyl alcohol (1.79 g, 67percent). (2) In a test tube for a microwave reaction, sodium methanesulfinate (1.44 g), copper(I) trifluoromethanesulfonate benzene complex (711 mg) and N, N'-dimethylethylenediamine (304 muL) were added to a solution of the compound (966 mg) obtained in the above described (1) in dimethylsulfoxide (19 mL), the air in the test tube was purged with nitrogen, then the test tube was sealed, and the mixture was stirred at 150C under microwave irradiation for 1 hour. After cooling to room temperature, the mixture was poured into an aqueous solution of saturated ammonium chloride, and the resultant mixture was stirred at room temperature for a while and then was extracted with ethyl acetate. The organic layer was washed with water and subsequently with brine, and was separated by a phase separator, and the solvent was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform/methanol = 97:3 to 91:9) to give the title compound (767 mg) as a colorless oily substance. 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 2.07 (t, J=5.81 Hz, 1 H) 3.07 (s, 3 H) 4.81 (d, J=5.75 Hz, 2 H) 7.37 - 7.43 (m, 1 H) 7.52 - 7.58 (m, 1 H) 7.72 - 7.76 (m, 1 H). MS ESI/APCI Multi posi: 227 [M+Na]+.To a 50 mL flask containing

Molecular Weight:205.02
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:203.95861
Monoisotopic Mass:203.95861
Topological Polar Surface Area:20.2
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes