1-(bromomethyl)-2-chloro-4-methoxybenzene

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

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

Conditions: temp:-72.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Chloro-N-methoxy-N-methyl-isonicotinamide (24.6 g, 0.127 mol) and 1-bromomethyl-2-chloro-4-methoxy-benzene [CAS Reg. No. 54788-17-9] (34.7 g, 0.147 mol) were dissolved in THF (720 ml), cooled down to −72° C. and treated over a period of 1.3 h with 1.6 M n-BuLi in hexanes (157 ml, 0.251 mol) without exceeding −70° C. The reaction mixture was stirred at −72° C. for 15 min, warmed up to −20° C. (duration: 35 min) and treated with saturated aqueous NH4Cl (400 ml). After 5 min, the reaction mixture was extracted twice with ethyl acetate. The combined organic phases were washed with saturated aqueous NH4Cl, dried over MgSO4, filtered off and concentrated in vacuo to yield an orange oil (46.5 g). The residue was purified by flash chromatography (600 g silica gel, ethyl acetate/heptane 1:1) to give the title compound as orange viscous oil (17.1 g). MS (m/e, neg. ion)=294.2 [M−H+]. without exceeding −70° C warmed up to −20° C. (duration: 35 min) After 5 min the reaction mixture was extracted twice with ethyl acetate The combined organic phases were washed with saturated aqueous NH4Cl dried over MgSO4 filtered off concentrated in vacuo

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

Procedure: Heat a solution of 2-chloro-4-methoxy-1-methyl-benzene (2.0 g, 13 mmol), N-bromosuccinimide (2.7 g, 15 mmol), and benzoyl peroxide (50 mg) in CCl4 (50 mL) to reflux and stir for 3 hr. Cool the reaction to room temperature and quench with water. Extract the aqueous with CH2Cl2, dry over MgSO4, and filter. Remove the solvent to afford 3.0 g (98%) of the desired product. to reflux Cool the reaction to room temperature quench with water Extract the aqueous with CH2Cl2 dry over MgSO4 filter Remove the solvent

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

Procedure: Heat a solution of 2-chloro-4-methoxy-1-methyl-benzene (2.0 g, 13 mmol), N-bromosuccinimide (2.7 g, 15 mmol), and benzoyl peroxide (50 mg) in CCl4 (50 mL) to reflux and stir for 3 hr. Cool the reaction to room temperature and quench with water. Extract the aqueous with CH2Cl2, dry over MgSO4, and filter. Remove the solvent to afford 3.0 g (98%) of the desired product. to reflux Cool the reaction to room temperature quench with water Extract the aqueous with CH2Cl2 dry over MgSO4 filter Remove the solvent

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

Procedure: 212 g (purity 82%) of 2-chloro-4-methoxybenzyl bromide in 900 ml of dichloromethane are reacted in the course of 4 h at 40° C. with 176 g of potassium cyanide in 675 ml of water and 15.5 g of tetrabutylammonium hydrogen sulfate. After working-up, 157 g of brownish oil are obtained (purity 79%).

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

Procedure: 186 g of 2-chloro-4-methoxytoluene are dissolved in 1000 ml of carbon tetrachloride and, together with 212 g of N-bromosuccinimide, heated at reflux for 2 h while 2.4 g of AIBN are added. The solid is filtered off and washed with a small amount of carbon tetrachloride, the filtrate is concentrated, and the residue which remains is fractionated. 252 g of orange oil are obtained (Purity 82%). heated are added The solid is filtered off washed with a small amount of carbon tetrachloride the filtrate is concentrated

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

Procedure: A mixture of 1-(bromomethyl)-2-chloro-4-methoxybenzene (1.0 g, 4.2 mmol), 6-methyl-2-sulfanylpyrimidin-4-ol (550 mg, 3.9 mmol), and triethylamine (585 μL, 4.2 mmol) in absolute ethanol (20 mL) was stirred at room temperature overnight. The product was recovered by filtration, washed with water (2×20 mL) and diethyl ether (2×20 mL), and dried in vacuo, affording the title compound (929 mg, 81% yield); 1H NMR (400 MHz, DMSO-d6): δ 2.07 (s, 3H), 3.76 (s, 3H), 4.41 (s, 2H), 6.00 (s (br), 1H), 6.89 (dd, 1H, J=2.5 Hz, 8.6 Hz), 7.07 (d, 1H, J=8.6 Hz), 7.52 (d, 1H, J=8.6 Hz); M+297. The product was recovered by filtration washed with water (2×20 mL) and diethyl ether (2×20 mL) dried in vacuo

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

Procedure: A mixture of 1-(bromomethyl)-2-chloro-4-methoxybenzene (1.0 g, 4.2 mmol), 6-methyl-2-sulfanylpyrimidin-4-ol (550 mg, 3.9 mmol), and triethylamine (585 μL, 4.2 mmol) in absolute ethanol (20 mL) was stirred at room temperature overnight. The product was recovered by filtration, washed with water (2×20 mL) and diethyl ether (2×20 mL), and dried in vacuo, affording the title compound (929 mg, 81% yield); 1H NMR (400 MHz, DMSO-d6): δ 2.07 (s, 3H), 3.76 (s, 3H), 4.41 (s, 2H), 6.00 (s (br), 1H), 6.89 (dd, 1H, J=2.5 Hz, 8.6 Hz), 7.07 (d, 1H, J=8.6 Hz), 7.52 (d, 1H, J=8.6 Hz); M+297. The product was recovered by filtration washed with water (2×20 mL) and diethyl ether (2×20 mL) dried in vacuo

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

Procedure: A mixture of 1-(bromomethyl)-2-chloro-4-methoxybenzene (1.0 g, 4.2 mmol), 6-methyl-2-sulfanylpyrimidin-4-ol (550 mg, 3.9 mmol), and triethylamine (585 μL, 4.2 mmol) in absolute ethanol (20 mL) was stirred at room temperature overnight. The product was recovered by filtration, washed with water (2×20 mL) and diethyl ether (2×20 mL), and dried in vacuo, affording the title compound (929 mg, 81% yield); 1H NMR (400 MHz, DMSO-d6): δ 2.07 (s, 3H), 3.76 (s, 3H), 4.41 (s, 2H), 6.00 (s (br), 1H), 6.89 (dd, 1H, J=2.5 Hz, 8.6 Hz), 7.07 (d, 1H, J=8.6 Hz), 7.52 (d, 1H, J=8.6 Hz); M+ 297. The product was recovered by filtration washed with water (2×20 mL) and diethyl ether (2×20 mL) dried in vacuo

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of zinc powder (1.67 g) in 1,2-dimethoxyethane (60 mL) was added tetrakis(triphenylphosphine)palladium(0) (295 mg). A suspension of the 3-methyl-2-oxo-2,3-dihydro-benzooxazole-5-carbonyl chloride (2.71 g) in 1,2-dimethoxyethane (60 mL) was slowly added over a period of 20 minutes. The mixture was cooled in an ice bath and a solution of 1-bromomethyl-2-chloro-4-methoxy-benzene (3.01 g, [CAS Reg. No. 54788-17-9]) in 1,2-dimethoxyethane (20 mL) was slowly added over a period of 30 minutes. The mixture was stirred for 30 minutes at 0° C. and then for 2 hours at r.t. The reaction mixture was poured into ice and basified with sat. NaHCO3. The aqueous phase was then extracted two times with ethyl acetate and the organic layers were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, CH2Cl2) to give the title compound as a light yellow solid (2.45 g, 55%). MS (neg. ion, m/e)=330.3 [(M−H)−]. was slowly added over a period of 20 minutes The mixture was cooled in an ice bath for 2 hours at r.t The aqueous phase was then extracted two times with ethyl acetate the organic layers were washed with brine dried over Na2SO4 filtered the solvent was evaporated The residue was purified by flash chromatography (silica gel, CH2Cl2)