6-bromo-2,2-dimethylchromene

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

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

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 16 g of 6-bromo-2,2-dimethyl-2H-chromene are dissolved in 100 ml of triethyl phosphite. 2 g of nickel chloride are added and the mixture is refluxed at 180° C. for 24 hours in an autoclave. After the remaining triethyl phosphite has been concentrated, the expected product distills at 130°-140° C. under 0.1 mm Hg. 11.5 g are collected. After the remaining triethyl phosphite has been concentrated the expected product distills at 130°-140° C. under 0.1 mm Hg 11.5 g are collected

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 16 g of 6-bromo-2,2-dimethyl-2H-chromene are dissolved in 100 ml of triethyl phosphite. 2 g of nickel chloride are added and the mixture is refluxed at 180° C. for 24 hours in an autoclave. After the remaining triethyl phosphite has been concentrated, the expected product distills at 130°-140° C. under 0.1 mm Hg. 11.5 g are collected. After the remaining triethyl phosphite has been concentrated the expected product distills at 130°-140° C. under 0.1 mm Hg 11.5 g are collected

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 16 g of 6-bromo-2,2-dimethyl-2H-chromene are dissolved in 100 ml of triethyl phosphite. 2 g of nickel chloride are added and the mixture is refluxed at 180° C. for 24 hours in an autoclave. After the remaining triethyl phosphite has been concentrated, the expected product distills at 130°-140° C. under 0.1 mm Hg. 11.5 g are collected. After the remaining triethyl phosphite has been concentrated the expected product distills at 130°-140° C. under 0.1 mm Hg 11.5 g are collected

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

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (−78° C.) stirring solution of 6-bromo-2,2-dimethyl-2H-chromene, which was prepared according to Chemistry and Biology, 2000, Vol. 7, p. 979, (567.7 mg, 2.38 mmol) in THF (7 mL) was added n-BuLi (2.88 M, 0.94 mL, 2.71 mmol). After completion of addition, the reaction mixture continued to stir at −78° C. After 25 minutes, (4-benzyloxy-3,5-dimethoxy-phenyl)-acetaldehyde (619.6 mg, 2.17 mmol) dissolved in THF (7.0 mL) was added. After completion of addition the reaction continued to stir for 15 minutes and was then quenched with saturated ammonium chloride. The aqueous layer was separated and extracted with ethyl acetate. All Combined organic layers were dried over sodium sulfate, filtered, and concentrated to yield a crude oil. The crude material was purified by silica gel chromatography (3:1 ethyl acetate:hexanes) to yield the desired product (200.5 mg, 20% yield). was prepared After completion of addition was added After completion of addition the reaction to stir for 15 minutes was then quenched with saturated ammonium chloride The aqueous layer was separated extracted with ethyl acetate were dried over sodium sulfate filtered concentrated to yield a crude oil The crude material was purified by silica gel chromatography (3:1 ethyl acetate:hexanes)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (−78° C.) stirring solution of 6-bromo-2,2-dimethyl-2H-chromene, which was prepared according to Chemistry and Biology, 2000, Vol. 7, p. 979, (567.7 mg, 2.38 mmol) in THF (7 mL) was added n-BuLi (2.88 M, 0.94 mL, 2.71 mmol). After completion of addition, the reaction mixture continued to stir at −78° C. After 25 minutes, (4-benzyloxy-3,5-dimethoxy-phenyl)-acetaldehyde (619.6 mg, 2.17 mmol) dissolved in THF (7.0 mL) was added. After completion of addition the reaction continued to stir for 15 minutes and was then quenched with saturated ammonium chloride. The aqueous layer was separated and extracted with ethyl acetate. All Combined organic layers were dried over sodium sulfate, filtered, and concentrated to yield a crude oil. The crude material was purified by silica gel chromatography (3:1 ethyl acetate:hexanes) to yield the desired product (200.5 mg, 20% yield). was prepared After completion of addition was added After completion of addition the reaction to stir for 15 minutes was then quenched with saturated ammonium chloride The aqueous layer was separated extracted with ethyl acetate were dried over sodium sulfate filtered concentrated to yield a crude oil The crude material was purified by silica gel chromatography (3:1 ethyl acetate:hexanes)

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

Procedure: 6-Bromo-2,2-dimethyl-2H-chromene is metallated at -78° C. using 2 equivalents of tert.-butyllithium and subsequently reacted with 2-trifluoromethylbenzaldehyde to give 2,2-dimethyl-6-(2-trifluoromethyl-hydroxybenzyl)-2H-chromene which is produced as an oil. is metallated at -78° C.

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

Procedure: 6-Bromo-2,2-dimethyl-2H-chromene is metallated at -78° C. using 2 equivalents of tert.-butyllithium and subsequently reacted with 2-trifluoromethylbenzaldehyde to give 2,2-dimethyl-6-(2-trifluoromethyl-hydroxybenzyl)-2H-chromene which is produced as an oil. is metallated at -78° C.

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1.5M solution of butyllithium in hexane (5.2 ml) was added to a stirred solution of 2,2-dimethyl-6-bromochromene [prepared by the procedure described in Bull. Chem. Soc. Jap., 1982, 55(4) 1153] (2.0 g, 8.4 mM) in sodium dried ether (24 ml). The mixture was stirred for 3 hours, then cooled to -20° C. and treated with excess gaseous sulphur dioxide, whereupon the lithium sulphinate salt immediately began to separate out as a solid. The resultant suspension was stirred rapidly for one hour and then allowed to attain ambient temperature. The solid precipitate of lithium 2,2-dimethylchromene-6-sulphinate was collected by filtration and washed with dry acetone and sodium dried ether. The lithium salt was then dissolved in water and the solution acidified to pH 1 and extracted with ethyl acetate. The combined extracts were dried (Na2SO4) and evaporated. The resultant 2,2-dimethylchromene-6-sulphinic acid was dissolved in methanol (10 ml) containing sodium methoxide (400 mg, 7.3 mmol). After 10 minutes, the methanol was removed in vacuo to leave a solid residue of sodium 2,2-dimethylchromene-6-sulphinate, which was dried by azeotropic distillation with toluene in vacuo and used directly in the above reaction. prepared by the procedure to separate out as a solid The resultant suspension was stirred rapidly for one hour to attain ambient temperature The solid precipitate of lithium 2,2-dimethylchromene-6-sulphinate was collected by filtration washed with dry acetone and sodium dried ether The lithium salt was then dissolved in water extracted with ethyl acetate The combined extracts were dried (Na2SO4) evaporated The resultant 2,2-dimethylchromene-6-sulphinic acid was dissolved in methanol (10 ml) After 10 minutes the methanol was removed in vacuo