2-Bromo-5-fluorobenzenemethanol

Colorless liquid

To a solution of compound A2-1 (75.0 g, 369 mmol) in EtOH (375 rnL) was added a solution OfNaBH(1) 200 g of Compound I was dissolved in 1400 ml of methanol, cooled to 5 ° C or less, and slowly added 18.1 g of sodium borohydride, and the temperature was raised to 20 ° C, and the reaction plate was sampled for 0.5 h. After the reaction is completed, the mixture is evaporated to a paddle shape under reduced pressure, and then added dropwise to 3000 ml of deionized water for crystallization, and stirred and filtered. Drying under reduced pressure gave Compound II in a yield of 92percent.6.24. 6.56. To a solution of compound A2-1 (75.0 g, 369 mmol) in EtOH (375 rnL) was added a solution OfNaBH4 (4.47 g, 118 mmol) in water (9 mL) at 0C, and the mixture was stirred at rt for 1 h. The mixture was treated with water and EtOAc, and extracted with EtOAc. The extract was washed with brine, dried over Na2SO4. The solvent was concentrated in vacuo to give 75.6 g of compound A2-2 (yield = 99.8 %) as a colorless solid. 1H NMR (CDCl3) delta 7.5O-7.46(1H, m), 7.29-7.25(1H, m), 6.92-6.85(1H, m), 4.72(2H, s).(1) 200 g of Compound I was dissolved in 1400 ml of methanol, cooled to 5 C or less, and slowly added 18.1 g of sodium borohydride, and the temperature was raised to 20 C, and the reaction plate was sampled for 0.5 h. After the reaction is completed, the mixture is evaporated to a paddle shape under reduced pressure, and then added dropwise to 3000 ml of deionized water for crystallization, and stirred and filtered. Drying under reduced pressure gave Compound II in a yield of 92%.To a solution of 2-bromo-5-fluorobenzaldehyde 71 (25.00g, 123.15mmol) in MeOH (200mL) was added NaBH4 (4.66g, 123.15mmol) portionwise at 0C, and the mixture was stirred at room temperature for 2.5h. Water was added, and the solvent was removed under reduced pressure to about a half volume. The mixture was poured into EtOAc and water. The organic layer was washed with brine and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure to give compound 72 (21.00g, 83%) as a white solid. 1H NMR (400MHz, Methanol-d4) delta 7.53 (dd, J=8.7, 5.2Hz, 1H), 7.30 (dd, J=9.7, 3.1Hz, 1H), 6.95 (td, J=8.4, 3.4Hz, 1H), 4.61 (s, 2H).To a solution of 3 (62.0 g, 293 mmol) in MeOH (400 mL) was added NaBH4 (5.57 g, 147 mmol) portionwise at 0 C., and the mixture was stirred at room temperature for 1 h. Water was added, and the solvent was removed under reduced pressure to about a half volume. The mixture was poured into EtOAc and water. The organic layer was washed with brine and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure to afford 4b, which was used for the next step without purification. To a solution of 4b (60.8 g, 293 mmol) and i-Pr2NEt (61 mL, 0.35 mol) in CH2Cl2 was added chloromethyl methyl ether (27 mL, 0.35 mmol) at 0 C., and the mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with CHCl3. The organic layer was washed with brine and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure to afford 5b (73.2 g, quant). 1H NMR (300 MHz, CDCl3) delta (ppm) 3.43 (s, 3H), 4.62 (s, 2H), 4.78 (s, 2H), 6.88 (td, J=8.5, 3.2 Hz, 1H), 7.25 (dd, J=9.6, 3.1 Hz, 1H), 7.48 (dd, J=8.8, 5.3 Hz, 1H).General procedure: The carbonyl compound (1 mmol) and NaBH4 (2 mmol) were taken in a two-neck round bottomed flask and flashed with nitrogen gas. Then 5 mL of methanol was added to it and stirred at room temperature for 1h. After completion of the reaction, methanol was evaporated under reduced pressure and then the reaction mixture was diluted with saturated ammonium chloride solution and extracted with ethyl acetate (3 x 20 mL). The combined organic layer was washed with brine, dried over anhydrous Na2SO4, evaporated under reduced pressure. Then the crude product was purified by column chromatography using silica gel (60-120 mesh) and hexane/EtOAc as eluent.Compound 34a (1.0 g, 5.0 mmol) was dissolved in 20 mL MeOH.Then NaBH4 (1.0 g, 5.6 mmol) was added under ice bath and reacted for 2 h.The reaction solution was concentrated by EA extraction and purified by silica gel column chromatography to afford compound 34b (1 g). 2-Bromo-5-fluorobenzylbromide (2.0 g, 7.46 mmol) was dissolved in dioxane (25 mL) and H2O (25 mL), and CaCO3 (3.84 g, 38.39 mmol) was added. The mixture was heated to reflux overnight. The solution was concentrated, and the residue was partitioned between H2O and CH2Cl2. The organic phase was washed with 1N HCl and brine, dried (MgSO4), filtered, and concentrated to afford the title compound. 1H NMR (CDCl3): delta2.00 (t, 1 H), 4.72 (d, 2 H), 6.85-6.92 (m, 1 H), 7.26 (dd, 1 H), 7.48 (dd, 1 H).

Molecular Weight:205.02
XLogP3:1.6
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