1-bromo-4-(methoxymethoxy)benzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromophenol (1.0 g, 5.8 mmol) in anhydrous THF (10 mL) was added NaH (60%, 254 mg, 6.4 mmol) at 0° C. After being stirred at the temperature for 0.5 h, MOM-Cl (698 mg, 8.7 mmol) was added to the mixture. The mixture was stirred at 0° C. for 0.5 h, warmed to room temperature for 2 h, quenched with water, and extracted with EtOAc. The organic layer was dried over Na2SO4, concentrated in vacuo, and purified by column chromatography (PE:EtOAc=50:1) to give 1-bromo-4-(methoxymethoxy)benzene (1 g, yield 80%). The mixture was stirred at 0° C. for 0.5 h quenched with water extracted with EtOAc The organic layer was dried over Na2SO4 concentrated in vacuo purified by column chromatography (PE:EtOAc=50:1)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a degassed solution of 1-bromo-4-(methoxymethoxy)benzene (360 mg, 1.66 mmol), pyridin-4-ylboronic acid (307 mg, 2.50 mmol), and Cs2CO3 (1.09 g, 3.35 mmol) in THF (5 mL) was added Pd(PPh3)4 (190 mg, 0.16 mmol). The reaction mixture was heated at 80° C. overnight and diluted with EtOAc (50 mL). It was washed with H2O (2×25 mL), dried over Na2SO4, and concentrated. Purification on a silica gel column gave the desired product as a white solid (265 mg). NMR (CDCl3): 8.63 (d, 2H), 7.67 (d, 2H), 7.47 (d, 2H), 7.16 (d, 2H), 5.24 (s, 2H), 3.52 (s, 3H). It was washed with H2O (2×25 mL) dried over Na2SO4 concentrated Purification on a silica gel column

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromophenol (0.50 g, 2.89 mmol) and dimethoxymethane (2.6 mL, 29.39 mmol) in DCM (60 mL) was added P2O5 (1.50 g, 10.57 mmol). The reaction mixture was stirred at for 1 h and insoluble precipitate was filtered off. Solid Na2CO3 was added to the solution and stirred for additional 10 min. The solid was filtered off and the solution was concentrated. Purification on a silica gel column gave the desired product as a clear oil (363 mg). NMR (CDCl3): 7.38 (d, 2H), 6.93 (d, 2H), 5.15 (s, 2H), 3.47 (s, 3H). was filtered off Solid Na2CO3 was added to the solution stirred for additional 10 min The solid was filtered off the solution was concentrated Purification on a silica gel column

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a reactor, 40 g of p-bromophenol and 200 ml of DMF (dimethylformamide) were charged, to which 10 g of a 60% NaH (sodium hydride) were gradually added to give a solution. To the solution, 18 g of methoxymethyl chloride were added dropwise with stirring at a temperature of 30° C. or lower, and reacted overnight at room temperature to give a reaction solution. The reaction solution was poured into water, extracted with benzene, washed with water, dried over sodium sulfate anhydride, and thereafter the solvent was evaporated and the residue was distilled under reduced pressure to give 38.4 g (Y., 79.3%) of 4-bromopheny methoxymethyl ether. b.p.; 65°-67° C./0.6 mmHg GC; 99.4% were gradually added to give a solution lower, and reacted overnight at room temperature to give a reaction solution extracted with benzene washed with water dried over sodium sulfate anhydride the solvent was evaporated the residue was distilled under reduced pressure

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a reactor, 40 g of p-bromophenol and 200 ml of DMF (dimethylformamide) were charged, to which 10 g of a 60% NaH (sodium hydride) were gradually added to give a solution. To the solution, 18 g of methoxymethyl chloride were added dropwise with stirring at a temperature of 30° C. or lower, and reacted overnight at room temperature to give a reaction solution. The reaction solution was poured into water, extracted with benzene, washed with water, dried over sodium sulfate anhydride, and thereafter the solvent was evaporated and the residue was distilled under reduced pressure to give 38.4 g (Y., 79.3%) of 4-bromopheny methoxymethyl ether. b.p.; 65°-67° C./0.6 mmHg GC; 99.4% were gradually added to give a solution lower, and reacted overnight at room temperature to give a reaction solution extracted with benzene washed with water dried over sodium sulfate anhydride the solvent was evaporated the residue was distilled under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Methoxymethoxy-1-bromobenzene was prepared from formaldehyde dimethyl acetal and 4-bromophenol by the method of Y. P. Yardley and H. Fletcher, Synthesis 1976, p. 244. The boiling point of this derivative is 54° to 56° C. at 0.1 hPa, and the yield is 49 percent theory. Fletcher, Synthesis 1976, p this derivative is 54° to 56° C. at 0.1 hPa

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Methoxymethoxy-1-bromobenzene was prepared from formaldehyde dimethyl acetal and 4-bromophenol by the method of Y. P. Yardley and H. Fletcher, Synthesis 1976, p. 244. The boiling point of this derivative is 54° to 56° C. at 0.1 hPa, and the yield is 49 percent theory. Fletcher, Synthesis 1976, p this derivative is 54° to 56° C. at 0.1 hPa