benzyl 2-bromo-2,2-difluoroacetate

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

Procedure: 1.60 g (14 mmol) of t-butoxypotassium was added to a solution prepared by dissolving 20.30 g (0.1 mol) of ethyl 2-bromo-2,2-difluoroacetate in 140 ml of benzyl alcohol and 1200 ml of hexane at 0° C. in a nitrogen atmosphere. The mixture was stirred at 0° C. for 1 hour. After confirming disappearance of the raw materials by thin-layer chromatography (TLC), the reaction was terminated by adding 120 ml of concentrated hydrochloric acid. The mixture was washed twice with water, washed twice with a saturated sodium chloride solution, and dried over anhydrous sodium sulfate. After evaporating the solvent under reduced pressure, the product was purified by column chromatography to obtain 15.37 g of benzyl 2-bromo-2,2-difluoroacetate shown by the following formula (yield: 58%). prepared the reaction was terminated by adding 120 ml of concentrated hydrochloric acid The mixture was washed twice with water washed twice with a saturated sodium chloride solution dried over anhydrous sodium sulfate After evaporating the solvent under reduced pressure the product was purified by column chromatography

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

Procedure: 1.60 g (14 mmol) of t-butoxypotassium was added to a solution prepared by dissolving 20.30 g (0.1 mol) of ethyl 2-bromo-2,2-difluoroacetate in 140 ml of benzyl alcohol and 1200 ml of hexane at 0° C. in a nitrogen atmosphere. The mixture was stirred at 0° C. for 1 hour. After confirming disappearance of the raw materials by thin-layer chromatography (TLC), the reaction was terminated by adding 120 ml of concentrated hydrochloric acid. The mixture was washed twice with water, washed twice with a saturated sodium chloride solution, and dried over anhydrous sodium sulfate. After evaporating the solvent under reduced pressure, the product was purified by column chromatography to obtain 15.37 g of benzyl 2-bromo-2,2-difluoroacetate shown by the following formula (yield: 58%). prepared the reaction was terminated by adding 120 ml of concentrated hydrochloric acid The mixture was washed twice with water washed twice with a saturated sodium chloride solution dried over anhydrous sodium sulfate After evaporating the solvent under reduced pressure the product was purified by column chromatography

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

Procedure: Triethylamine (3.5 mL; 2.5 g; 25 mmol) was added using a syringe to a stirred mixture of the crude product of 3a (8.6 g; 20 mmol) and 5-(Cbz-amino)-4-oxopentanoic acid (6.63 g; 25 mmol) in dry acetonitrile (100 mL). The mixture was refluxed for 18 h, then the solvent was evaporated and the dark red residue was dissolved in diethyl ether (100 mL) and 0.5 M HCl (100 mL). After mixing thoroughly, the ether layer was washed with water (2×15 mL), saturated NaHCO3 (2×15 mL), and saturated NaCl solution (1×15 mL), then dried (MgSO4). After filtration and evaporation, the residue was purified by flash chromatography on a 60×55 mm silica gel 60 column eluted with dichloromethane-diethyl ether (9:1) (1000 mL), collecting 10×75 mL fractions. After evaporation of fractions 2-5 and vacuum-drying (0.02 mm Hg), 6.7 g (74%) product was obtained (red-orange solid mp 48-50° C.). The mixture was refluxed for 18 h the solvent was evaporated the dark red residue was dissolved in diethyl ether (100 mL) After mixing thoroughly the ether layer was washed with water (2×15 mL), saturated NaHCO3 (2×15 mL), and saturated NaCl solution (1×15 mL) dried (MgSO4) After filtration and evaporation the residue was purified by flash chromatography on a 60×55 mm silica gel 60 column eluted with dichloromethane-diethyl ether (9:1) (1000 mL) collecting 10×75 mL fractions After evaporation of fractions 2-5 vacuum-drying (0.02 mm Hg)

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

Procedure: This compound was prepared according to Example 2a from bromodifluoroacetic acid (9.82 g; 68.7 mmol), benzyl alcohol (7.0 g; 65 mmol), and p-toluenesulphonic acid monohydrate (50 mg) in cyclohexane (120 mL). The crude product obtained after evaporation was used as is without any further workup in 3b. This compound was prepared

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

Procedure: 1.60 g (14 mmol) of t-butoxypotassium was added to a solution prepared by dissolving 20.30 g (0.1 mol) of ethyl 2-bromo-2,2-difluoroacetate in 140 ml of benzyl alcohol and 1200 ml of hexane at 0° C. in a nitrogen atmosphere. The mixture was stirred at 0° C. for 1 hour. After confirming disappearance of the raw materials by thin-layer chromatography (TLC), the reaction was terminated by adding 120 ml of concentrated hydrochloric acid. The mixture was washed twice with water, washed twice with a saturated sodium chloride solution, and dried over anhydrous sodium sulfate. After evaporating the solvent under reduced pressure, the product was purified by column chromatography to obtain 15.37 g of benzyl 2-bromo-2,2-difluoroacetate shown by the following formula (yield: 58%). prepared the reaction was terminated by adding 120 ml of concentrated hydrochloric acid The mixture was washed twice with water washed twice with a saturated sodium chloride solution dried over anhydrous sodium sulfate After evaporating the solvent under reduced pressure the product was purified by column chromatography