benzyl 2-bromopropanoate

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: 20.0 g (0.13 moles) of 2-bromopropionic acid were stirred with 14.1 g (0.13 moles) of benzyl alcohol in dry methylene chloride at 5°-10° C., before 0.16 g (1.3e-3 moles) of 4-dimethylaminopyridine (DMAP) were added. The temperature was raised to ~15° C. before a solution of dicyclohexylcarbodiimide (DCC) (26.7 g, 0.13 moles) in dry methylene chloride was added dropwise. The solution was added at a rate as to not increase the reaction temperature above 35° C. After the imide addition was complete, the reaction proceeded at 25° C. for several hours or until infrared spectroscopy analysis indicated the absence of a carboxylic acid stretch at 1730 cm-1. Upon completion, the reaction mixture was filtered under vacuum to remove the dicyclohexyl urea (DCU) byproduct and the filtrate was extracted once with water, once with 5% acetic acid solution (to remove DMAP) and again with water. The organic layer was dried over anhydrous magnesium sulfate before being filtered and concentrated under reduced pressure. Yield was 25 g (72%) of a mixture of Benzyl-2-bromopropionate and Benzyl-2-chloropropionate. were added was added dropwise The solution was added at a rate as to not increase the reaction temperature above 35° C the reaction proceeded at 25° C. for several hours Upon completion, the reaction mixture was filtered under vacuum to remove the dicyclohexyl urea (DCU) byproduct the filtrate was extracted once with water, once with 5% acetic acid solution (to remove DMAP) and again with water The organic layer was dried over anhydrous magnesium sulfate before being filtered concentrated under reduced pressure

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

Procedure: 2-Bromopropionic acid (750 g, 4.90 moles) and benzyl alcohol (600 g, 3.55 moles) were dissolved in methylene chloride (1500 ml). To the resulting solution was added concentrated sulfuric acid (10 ml). The resulting solution was heated to a gentle reflux for two days, water separating during this time. Water (500 ml) was added and the layers were separated. The methylene chloride was washed with saturated sodium bicarbonate and the layers were separated. The organic layer was washed with water, dried over magnesium sulfate, filtered and evaporated to give a colorless oil which was vacuum distilled to give the pure product as a colorless oil (742 g, 86%). The resulting solution was heated to a gentle reflux for two days the layers were separated The methylene chloride was washed with saturated sodium bicarbonate the layers were separated The organic layer was washed with water dried over magnesium sulfate filtered evaporated to give a colorless oil which distilled

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

Procedure: 2,5-Dibromophenol (53 g) and benzyl 2-bromopropionate (48.6 g) in methyl iso-butyl ketone (250 ml) containing suspended potassium carbonate (13.8 g) was heated under reflux with stirring overnight. The mixture was cooled to 40°, 5% sodium hydroxide solution (100 ml) was added, and the mixture was stirred to dissolve the solid potassium bromide. The aqueous phase was separated with fresh methyl iso-butyl ketone (50 ml). The combined extracts were washed with water (50 ml), dried, and evaporated under reduced pressure. The residue was distilled and the benzyl (2,5-dibromophenoxy)propionate collected at 180°-185°/0.5 Torr. On cooling, the distillate solidified and had a melting point of 52° C. Compounds 1, 5, 6, 14 to 16, 18 to 20, 22 and 23 were made by a similar procedure. was heated under reflux The mixture was cooled to 40° the mixture was stirred The aqueous phase was separated with fresh methyl iso-butyl ketone (50 ml) The combined extracts were washed with water (50 ml) dried evaporated under reduced pressure The residue was distilled the benzyl (2,5-dibromophenoxy)propionate collected at 180°-185°/0.5 Torr On cooling

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

Procedure: 2-Bromopropionyl chloride (213.4 g) was added dropwise to benzyl alcohol (145.8 g) with stirring under a stream of nitrogen, keeping the temperature of the reaction mixture below 30° C. by cooling with cold water. When all the acid chloride has been added, the mixture was stirred for another two hours at ambient temperature. The reaction mixture was then diluted with diethyl ether (200 ml) and washed with water until free of acid. The ethereal solution was dried and evaporated and the residue distilled to give benzyl 2-bromopropionate, b.p. 82°-85°/0.5 Torr. the temperature of the reaction mixture below 30° C. the mixture was stirred for another two hours at ambient temperature washed with water until free of acid The ethereal solution was dried evaporated the residue distilled

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

Procedure: 2,5-Dibromophenol (53 g) and benzyl 2-bromopropionate (48.6 g) in methyl iso-butyl ketone (250 ml) containing suspended potassium carbonate (13.8 g) was heated under reflux with stirring overnight. The mixture was cooled to 40°, 5% sodium hydroxide solution (100 ml) was added, and the mixture was stirred to dissolve the solid potassium bromide. The aqueous phase was separated with fresh methyl iso-butyl ketone (50 ml). The combined extracts were washed with water (50 ml), dried, and evaporated under reduced pressure. The residue was distilled and the benzyl (2,5-dibromophenoxy)propionate collected at 180°-185°/0.5 Torr. On cooling, the distillate solidified and had a melting point of 52° C. Compounds 1, 5, 6, 14 to 16, 18 to 20, 22 and 23 were made by a similar procedure. was heated under reflux The mixture was cooled to 40° the mixture was stirred The aqueous phase was separated with fresh methyl iso-butyl ketone (50 ml) The combined extracts were washed with water (50 ml) dried evaporated under reduced pressure The residue was distilled the benzyl (2,5-dibromophenoxy)propionate collected at 180°-185°/0.5 Torr On cooling

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

Procedure: 2-Bromopropionyl chloride (213.4 g) was added dropwise to benzyl alcohol (145.8 g) with stirring under a stream of nitrogen, keeping the temperature of the reaction mixture below 30° C. by cooling with cold water. When all the acid chloride has been added, the mixture was stirred for another two hours at ambient temperature. The reaction mixture was then diluted with diethyl ether (200 ml) and washed with water until free of acid. The ethereal solution was dried and evaporated and the residue distilled to give benzyl 2-bromopropionate, b.p. 82°-85°/0.5 Torr. the temperature of the reaction mixture below 30° C. the mixture was stirred for another two hours at ambient temperature washed with water until free of acid The ethereal solution was dried evaporated the residue distilled

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

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

Procedure: 2-Bromopropionic acid (750 g, 4.90 moles) and benzyl alcohol (600 g, 3.55 moles) were dissolved in methylene chloride (1500 ml). To the resulting solution was added concentrated sulfuric acid (10 ml). The resulting solution was heated to a gentle reflux for two days, water separating during this time. Water (500 ml) was added and the layers were separated. The methylene chloride was washed with saturated sodium bicarbonate and the layers were separated. The organic layer was washed with water, dried over magnesium sulfate, filtered and evaporated to give a colorless oil which was vacuum distilled to give the pure product as a colorless oil (742 g, 86%). The resulting solution was heated to a gentle reflux for two days the layers were separated The methylene chloride was washed with saturated sodium bicarbonate the layers were separated The organic layer was washed with water dried over magnesium sulfate filtered evaporated to give a colorless oil which distilled

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

Procedure: Triethylamine was added drop-wise to a stirred solution of 5-(Cbz-amino)-4-oxopentanoic acid (4.00 g; 15.0 mmol) and the product of 2a (3.65 g; 15.0 mmol) in ethyl acetate (50 mL). The stirred mixture was refluxed for 2 days under argon. After cooling to ambient temperature, 0.5 M HCl solution (50 mL) was added and the mixture was shaken thoroughly. The aqueous layer was extracted with ethyl acetate (2×20 mL). The combined ethyl acetate solutions were washed with saturated NaHCO3 solution (2×15 mL) and saturated NaCl solution (1×15 mL), then dried (MgSO4). After filtration and evaporation an amber oil was obtained that was purified by flash chromatography on a 60×55 mm silica gel 60 column eluted with ethyl acetate-hexane (1:1) (1000 mL), collecting 8×100 mL fractions. Evaporation of fractions 3-5 resulted in 4.92 g (77%) product (oil). The stirred mixture was refluxed for 2 days under argon The aqueous layer was extracted with ethyl acetate (2×20 mL) The combined ethyl acetate solutions were washed with saturated NaHCO3 solution (2×15 mL) and saturated NaCl solution (1×15 mL) dried (MgSO4) After filtration and evaporation an amber oil was obtained that was purified by flash chromatography on a 60×55 mm silica gel 60 column eluted with ethyl acetate-hexane (1:1) (1000 mL) collecting 8×100 mL fractions Evaporation of fractions 3-5

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

Procedure: A mixture of 2-bromopropanoic acid (15.3 g; 100 mmol), benzyl alcohol (13.0 g; 120 mmol) and p-toluenesulphonic acid monohydrate (50 mg) in cyclohexane (200 mL) was refluxed in a Dean-Stark apparatus for 19 h. The reaction mixture was cooled to ambient temperature, washed with saturated NaHCO3 solution (1×30 mL), water (1×30 mL) and saturated NaCl solution (1×30 mL). After drying (MgSO4), filtration, and evaporation, the residue was vacuum-distilled. 25.4 g (87%) product was obtained (colourless liquid, by 111-113° C./1.1 mm Hg). was refluxed in a Dean-Stark apparatus for 19 h washed with saturated NaHCO3 solution (1×30 mL), water (1×30 mL) and saturated NaCl solution (1×30 mL) After drying (MgSO4), filtration, and evaporation the residue was vacuum-distilled