1-Bromo-4-(2-methoxyethoxy)benzene

General procedure: KStep 1-Preparation 1-Bromo-4-(2-methoxy-ethoxy)-benzene (42)To a solution of 4-bromophenol (41, 5.0 g, 28.9 mmol) in dimethylformamide (15 mL) were added potassium carbonate (4.40 g, 31.8 mmol) and 1-bromo-2-methoxyethane (5.00 g, 36.0 mmol) under an atmosphere of nitrogen. The reaction mixture was stirred at ambient temperature overnight and concentrated under reduced pressure. The residue was slurried in ethyl acetate (50 mL) and filtered. The filtrate was washed with saturated sodium bicarbonate solution, dried over magnesium sulfate and filtered. Silica gel column chromatography (0-10percent ethyl acetate in hexanes) gave the desired compound as a colorless oil (42, 3.2 g, 48percent).To a solution of 4-bromophenol (646, 5.0 g, 28.9 mmol) in dimethylformamide (15 mL) were added potassium carbonate (4.40 g, 31.8 mmol) and l-bromo-2-methoxyethane (5.00 g, 36.0 mmol) under an atmosphere of nitrogen. The reaction mixture was stirred at ambient temperature overnight and concentrated under reduced pressure. The residue was slurried in ethyl acetate (50 mL) and filtered. The filtrate was washed with saturated sodium bicarbonate solution, dried over magnesium sulfate and filtered. Silica gel column chromatography (0-10percent ethyl acetate in hexanes) gave the desired compound as a colorless oil (647, 3.2 g, 48percent).In an ice bath and argon protection conditions, 1.82g (10mmol) of (4- (2-methoxyethoxy) benzyl alcohol to 10mLOf anhydrous diethyl ether, the 4.05g (15mmol) of phosphorus tribromide dissolved in 10mL of anhydrous diethyl ether, a constant slow down funnelWas added dropwise to the above solution returned to room temperature after the addition was complete stirring, TLC tracking point disappears reaction to the raw material, the reaction was stopped, the iceUnder conditions with 25mL water bath to quench the reaction, the organic layer was dried over anhydrous sodium sulfate, the solvent was spin-dry as a colorless liquid (compound C), The yield was 90.3percent.4-Bromophenol (8.65 g; 0.05 mol), 2-methoxyethanol (1.1 eq. ; 0.055 mol; 4.36 ml) and triphenylphosphine (1.1 eq. ; 0.055 mol; 14.4 g) are dissolved in 210 ml of toluene. The reaction medium is brought to 54°C and diisopropyl azo- dicarboxylate (1.0 eq. ; 0.05 mol; 10.1 g) dissolved in 21 ml of toluene is added dropwise. The reaction medium is left at 54°C for one hour and then overnight at room temperature, and is then evaporated to dryness. The crude product is puri- fied by flash chromatography on silica on a gradient of heptane comprising 0-100percent DCM to give 9.6 g of the expected product in the form of an oil. TLC (1/4 heptane/DCM) : Rf = 0.46 Yld = 83.1 percent A mixture of tert-butyl piperidin-4-ylcarbamate (2.3 g, 10 mmol) , 1-bromo-4- (2-methoxyethoxy) benzene (2 g, 10 mmol) , Pd 2 (dba) 3 (0.905 g, 1 mmol) , X-phos (0.952 g, 2 mmol) and Cs 2CO 3 (6.52 g, 20 mmol) in toluene (30 mL) was stirred at 120 for 3 hours under N 2. The reaction was concentrated to give the residue, which was treated with EtOAc/H 2O (50 mL/20 mL) . The organic layer was separated, washed with brine, dried over Na 2SO 4, concentrated and purified by column chromatography (petroleum ether/EtOAc=8: 13: 1) to give the target compound (0.9 g, 25.8%) as yellow oil. MS: M/e 351 (M+1) +.General procedure: K2CO3 (18 mmol, 2.5 g) was suspended in 15 mL of DMF. The phenol (6.0 mmol) and the alkyl halide (6.6 mmol) were added subsequentially and the suspension was stirred overnight at 60 C. The reaction mixture was diluted with 50 mL demiwater and the resulting reaction mixture was extracted with with EtOAc (3 x 30 mL). The combined organic layers were, washed with brine (1 x 50 mL), dried over Na2SO4 and filtered. The solvent was evaporated under reduced pressure to give the product in high purity.Step 1-Preparation 1-Bromo-4-(2-methoxy-ethoxy)-benzene (42)To a solution of 4-bromophenol (41, 5.0 g, 28.9 mmol) in dimethylformamide (15 mL) were added potassium carbonate (4.40 g, 31.8 mmol) and 1-bromo-2-methoxyethane (5.00 g, 36.0 mmol) under an atmosphere of nitrogen. The reaction mixture was stirred at ambient temperature overnight and concentrated under reduced pressure. The residue was slurried in ethyl acetate (50 mL) and filtered. The filtrate was washed with saturated sodium bicarbonate solution, dried over magnesium sulfate and filtered. Silica gel column chromatography (0-10% ethyl acetate in hexanes) gave the desired compound as a colorless oil (42, 3.2 g, 48%).To a solution of 4-bromophenol (646, 5.0 g, 28.9 mmol) in dimethylformamide (15 mL) were added potassium carbonate (4.40 g, 31.8 mmol) and l-bromo-2-methoxyethane (5.00 g, 36.0 mmol) under an atmosphere of nitrogen. The reaction mixture was stirred at ambient temperature overnight and concentrated under reduced pressure. The residue was slurried in ethyl acetate (50 mL) and filtered. The filtrate was washed with saturated sodium bicarbonate solution, dried over magnesium sulfate and filtered. Silica gel column chromatography (0-10% ethyl acetate in hexanes) gave the desired compound as a colorless oil (647, 3.2 g, 48%).Part A: Preparation of To a room temperature solution of 4-bromophenol (5 g, 28.9 mmol) in 15 mL DMF under N2 was added 2-bromoethyl methyl ether (5 g, 36.4 mmol) and potassium carbonate (4.4 g, 31.8 mmol). The resulting solution was stirred overnight at ambient temperature under N2. Afterward, no starting material remained. The mixture was concentrated, partially dissolved in ethyl acetate (50 mL), and filtered. The filtrate was concentrated under reduced pressure, affording 5.6 g of crude oil. 1H NMR and mass spectrometry (MNa+=287.0) were consistent with the desired product.

Molecular Weight:231.09
XLogP3:2.4
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:4
Exact Mass:229.99424
Monoisotopic Mass:229.99424
Topological Polar Surface Area:18.5
Heavy Atom Count:12
Complexity:111
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes