1-bromo-2-(diethoxymethyl)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: A mixture of 2-bromobenzaldehyde (33.2 g), triethyl orthoformate (29 g) and powdered ammonium chloride (0.379 g) in ethanol (30 ml) was stirred for eight hours at room temperature. The resulting suspension was filtered and the filtrate evaporated. The resulting yellow oil was distilled at reduced pressure to give the title compound (31 g). b.p. 63° C. 0.3 mm Hg. T.l.c. (Petrol/diethyl ether, 6:1) Rf=0.6. The resulting suspension was filtered the filtrate evaporated The resulting yellow oil was distilled at reduced pressure

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

Procedure: To a mechanically stirred solution of 1-bromo-2-(diethoxymethyl)benzene (266 g) in dry diethyl ether (1.5 ) cooled to −70° C. under nitrogen was added a 2.5M solution of n-butyl lithium in hexanes (414 mL) dropwise over 30 min. The reaction mixture was stirred at a temperature less than −60° C. for 45 min then a solution of 4-bromo-2-fluorobenzaldehyde in dry diethyl ether (1.5 ) was added dropwise over 1 h maintaining the low temperature. The cooling bath was removed allowing the reaction to warm to +10° C. over 3 h. The reaction was quenched by the addition of water (500 mL). Organic layer was separated and the aqueous layer washed with ethyl acetate (2×500 mL). Combined organic layers were washed with brine then dried over anhydrous sodium sulfate and evaporated to yield the title product (371.1 g) as a yellow oil. maintaining the low temperature The cooling bath was removed the reaction to warm to +10° C. over 3 h The reaction was quenched by the addition of water (500 mL) Organic layer was separated the aqueous layer washed with ethyl acetate (2×500 mL) Combined organic layers were washed with brine then dried over anhydrous sodium sulfate evaporated

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

Procedure: To a mechanically stirred solution of 1-bromo-2-(diethoxymethyl)benzene (266 g) in dry diethyl ether (1.5 ) cooled to −70° C. under nitrogen was added a 2.5M solution of n-butyl lithium in hexanes (414 mL) dropwise over 30 min. The reaction mixture was stirred at a temperature less than −60° C. for 45 min then a solution of 4-bromo-2-fluorobenzaldehyde in dry diethyl ether (1.5 ) was added dropwise over 1 h maintaining the low temperature. The cooling bath was removed allowing the reaction to warm to +10° C. over 3 h. The reaction was quenched by the addition of water (500 mL). Organic layer was separated and the aqueous layer washed with ethyl acetate (2×500 mL). Combined organic layers were washed with brine then dried over anhydrous sodium sulfate and evaporated to yield the title product (371.1 g) as a yellow oil. maintaining the low temperature The cooling bath was removed the reaction to warm to +10° C. over 3 h The reaction was quenched by the addition of water (500 mL) Organic layer was separated the aqueous layer washed with ethyl acetate (2×500 mL) Combined organic layers were washed with brine then dried over anhydrous sodium sulfate evaporated

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

Procedure: To a solution of 10.4 g of 2-bromobenzaldehyde diethyl acetal in 200 ml of dry diethyl ether at −65° C. was added 27.5 ml of a 1.6 M solution of butyllithium in hexanes. The solution was stirred at this temperature for 30 min. then slowly warmed to −40° C. when 3.4 ml of dimethylformamide was added dropwise. The reaction was warmed to room temperature then 100 ml of water was added and the organic layer was separated. The aqueous layer was extracted with two 100 ml portions of ether and the combined organic extracts were dried over sodium sulfate and evaporated to give 8.5 g of 2-formylbenzaldehyde diethylacetal as an oil; 1H-NMR (200 MHz, CDCl3) d 5.06 (CHOEt). was added dropwise the organic layer was separated The aqueous layer was extracted with two 100 ml portions of ether the combined organic extracts were dried over sodium sulfate evaporated

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

Procedure: A stirred solution of 10.6 g of 2-bromobenzaldehyde diethyl acetal in 100 ml of diethyl ether was cooled to −40° C. To this cold solution was added rapidly 46 ml of a 1.2 M solution of butyllithium in hexane. The solution was warmed to 0° C. over 30 min. The solution was cooled down to −40° C. and a solution of 11.9 g of N-Methoxy-N-methyl-4-chloro-2-fluorobenzamide in 100 ml of diethyl ether added by cannular. The solution was warmed to 0° C. and stirred for 0.75 h then quenched by the addition of 100 ml of water and 200 ml of ether added. The organic layer was separated and the aqueous layer was extracted with 200 ml of ether. The combined organic layers were dried over sodium sulfate and evaporated to yield 19.6 g of crude [2-(diethoxymethyl)-phenyl](4-chloro-2-fluorophenyl)-methanone as a gum, GC-M.S. (E.I.) (M/Z): 336 [M]+. The solution was cooled down to −40° C. The solution was warmed to 0° C. then quenched by the addition of 100 ml of water and 200 ml of ether added The organic layer was separated the aqueous layer was extracted with 200 ml of ether The combined organic layers were dried over sodium sulfate evaporated

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

Procedure: A stirred solution of 10.6 g of 2-bromobenzaldehyde diethyl acetal in 100 ml of diethyl ether was cooled to −40° C. To this cold solution was added rapidly 46 ml of a 1.2 M solution of butyllithium in hexane. The solution was warmed to 0° C. over 30 min. The solution was cooled down to −40° C. and a solution of 11.9 g of N-Methoxy-N-methyl-4-chloro-2-fluorobenzamide in 100 ml of diethyl ether added by cannular. The solution was warmed to 0° C. and stirred for 0.75 h then quenched by the addition of 100 ml of water and 200 ml of ether added. The organic layer was separated and the aqueous layer was extracted with 200 ml of ether. The combined organic layers were dried over sodium sulfate and evaporated to yield 19.6 g of crude [2-(diethoxymethyl)-phenyl](4-chloro-2-fluorophenyl)-methanone as a gum, GC-M.S. (E.I.) (M/Z): 336 [M]+. The solution was cooled down to −40° C. The solution was warmed to 0° C. then quenched by the addition of 100 ml of water and 200 ml of ether added The organic layer was separated the aqueous layer was extracted with 200 ml of ether The combined organic layers were dried over sodium sulfate evaporated

Conditions: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 345 g of 2-bromobenzaldehyde diethyl acetal in 3 l of dry tetrahydofuran was cooled to −40° C. In one portion, 913 ml of a 1.6 M solution of butyllithium in hexane were added under vigorous stirring. The resulting solution was stirred for 0.5 h at −25° C., after which a solution of 140 ml of 2-fluorobenzaldehyde in 350 ml tetrahydrofuran was added drop-wise. In a period of 4 h, the mixture was allowed to reach room temperature. The resulting mixture was pored upon ice-water and extracted several times with ethyl acetate. The organic layers were combined, washed with water, dried over magnesium sulphate and evaporated to dryness under reduced pressure to yield 404 g of 2-(diethoxymethyl)-α-(2-fluorophenyl)-benzenemethanol as an oil, M.S. (C.I.) (M/Z): 305 [M+H]+. In a period of 4 h to reach room temperature extracted several times with ethyl acetate washed with water dried over magnesium sulphate evaporated to dryness under reduced pressure

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