3-(BROMOMETHYL)BENZALDEHYDE

Synthesis of Compounds 60 and 61To a solution of 3-(bromomethyl)benzonitrile (212mg, 1.081 mmol) in 2.5mL Toluene was added dropwise 1M DIBAL-H in THF (1.5 ml, 1.5 mmol) at 0° C. After stirring at 0°C for 2 h the reaction was diluted with DCM and IN aq. HCl and stirred for 1 hour. The organic layer was washed with brine, dried over sodium sulfate, and concentrated yielding the titled compound as an orange oil. (200mg, 0.970 mmol, 93percent yield)3- (Bromomethyl) benzonitrile (1.0 g, 5.10 mmol) was dissolved in toluene (17 L), cooled to 0 C and 1.5 M DIBAL (4.08 L, 6.12 mmol) dissolved in toluene was slowly added dropwise. The reaction solution was stirred at 0 ° C for 1.5 hours, and 1N HCl solution was slowly added thereto.The reaction solution was diluted with CH2Cl2 and washed with water. The organic solvent was dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (n-Hex / EtOAc = 9/1) to obtain the target compound 3- (bromomethyl) benzaldehyde (880 mg, 88percent).Step 1:N-Bromosuccinimide (NBS, 19.6 g) was added to a solution of 2a or 2b (10.0 g) in dichloromethane(120 mL). Triphenylphosphine (2.0 equiv, 38.5 g, 0.146 mol) was divided into four equal aliquots andan aliquot was added to the reaction every 30 min. After the reaction was completed, the solution wasmixed with cold water (120 mL). The aqueous phase was extracted two times with dichloromethaneand the organic phase was washed with a saturated NaCl solution and dried over Na2SO4 for 8 h.The mixture was purified by silica gel chromatography with petroleum ether–ethyl acetate = 25:1 aseluent to give compound 3a 8.5 g (58.0percent yield) and 3b 6.8 g (46.8percent yield), respectively.Take a 500mL eggplant flask, peeled and weighed 10.0g intermediate II-2 (0.073mol; 1.0equiv), 1b was dissolved by adding 150 mL of methylene chloride and 19.6 g of N-bromosuccinimide solid was added with stirring.Then ice-bath conditions to the eggplant-shaped flask was added in four batches of triphenylphosphine solids, a total of 38.5g (0.146mol; 2.0equiv), each batch interval of half an hour until triphenylphosphine plus Bi, remove the ice bath , The reaction was continued at room temperature for more than 3h, TLC TLC plate, UV analyzer (254nm) to monitor the progress of the reaction.After the raw material point II-2 disappears, the reaction is stopped and the reaction solution is poured into a beaker containing 150 ml of cold water.The aqueous phase was then poured into a separatory funnel mixture, the aqueous phase was extracted with 150 ml of methylene chloride, The combined dichloromethane layers were washed with saturated aqueous sodium chloride solution. Then, The organic phase is dried over anhydrous sodium sulphate or anhydrous magnesium sulphate overnight. Filter out the desiccant, Weigh about 60-100 mesh silica gel powder about 15g added to the filtrate, steaming to dry sand, Silica gel column chromatography, the elution system of choice for the petroleum ether: ethyl acetate = 99: 1, The resulting benzylic alcohol hydroxy-brominated reaction product was collected to give 6.8 g of III-2 as a white solid in a yield of 46.8percent.Take a 500mL eggplant-shaped bottle, Peel 10.0 g of intermediate II-2 (0.073 mol; 1.0 equiv).Dissolve 1b by adding 150 mL of dichloromethane.19.6 g of N-bromosuccinimide solid was added with stirring.Then, triphenylphosphine was added to the eggplant flask in four batches under ice-cooling conditions.A total of 38.5g (0.146mol; 2.0equiv), Each batch is separated by half an hour.After triphenylphosphine is added, Remove the ice bath, Continue to react at room temperature for more than 3 hours, Thin layer TLC board, An ultraviolet analyzer (254 nm) monitors the progress of the reaction. After the material point of II-2 disappears, Stop the reaction, Pour the reaction solution into a beaker containing 150 ml of cold water.Then, the aqueous organic phase mixture is poured into a separatory funnel for extraction.The aqueous phase is extracted with 150 ml of dichloromethane.Combine the dichloromethane layer, Add saturated aqueous sodium chloride solution.Then, The organic phase was dried over anhydrous sodium sulfate or anhydrous magnesium sulfate overnight.Filter out the desiccant, Weigh about 15g of 60-100 mesh silica gel powder into the filtrate.Rotary to dry sand, Silica gel column chromatography separation, The elution system selected was petroleum ether:ethyl acetate = 99:1.The resulting benzylic hydroxyl alcohol bromo reaction product is collected, A total of 6.8 g of III-2 white solid was obtained.Yield: 46.8percent.Compound 8

Molecular Weight:199.04
XLogP3:2.1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:2
Exact Mass:197.96803
Monoisotopic Mass:197.96803
Topological Polar Surface Area:17.1
Heavy Atom Count:10
Complexity:114
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes