tert-butyl 2-hydroxy-2-methylpropanoate

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: To a solution (22 mL) of tert-butyl 2-hydroxy-2-methylpropanoate (1.0 g) in N,N-dimethylformamide was added sodium hydride (250 mg) under an ice bath, and the mixture was stirred at room temperature for 1 hour. Thereafter, under an ice bath, 2-(3-bromopropoxy)tetrahydro-2H-pyran (0.88 mL) was added dropwise, and the mixture was stirred at room temperature overnight. To the reaction mixture were added water and 1N hydrochloric acid under an ice bath, followed by extraction with t-butyl methyl ether. The organic layer was sequentially washed with an aqueous saturated sodium bicarbonate solution and an aqueous saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:1) to obtain the title compound having the following physical property values, as a mixture (400 mg) with tert-butyl 2-hydroxy-2-methylpropanoate. the mixture was stirred at room temperature overnight followed by extraction with t-butyl methyl ether The organic layer was sequentially washed with an aqueous saturated sodium bicarbonate solution an aqueous saturated sodium chloride solution, dried with anhydrous sodium sulfate concentrated The residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:1)

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

Procedure: To a solution (22 mL) of tert-butyl 2-hydroxy-2-methylpropanoate (1.0 g) in N,N-dimethylformamide was added sodium hydride (250 mg) under an ice bath, and the mixture was stirred at room temperature for 1 hour. Thereafter, under an ice bath, 2-(3-bromopropoxy)tetrahydro-2H-pyran (0.88 mL) was added dropwise, and the mixture was stirred at room temperature overnight. To the reaction mixture were added water and 1N hydrochloric acid under an ice bath, followed by extraction with t-butyl methyl ether. The organic layer was sequentially washed with an aqueous saturated sodium bicarbonate solution and an aqueous saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:1) to obtain the title compound having the following physical property values, as a mixture (400 mg) with tert-butyl 2-hydroxy-2-methylpropanoate. the mixture was stirred at room temperature overnight followed by extraction with t-butyl methyl ether The organic layer was sequentially washed with an aqueous saturated sodium bicarbonate solution an aqueous saturated sodium chloride solution, dried with anhydrous sodium sulfate concentrated The residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:1)

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

Procedure: To a solution of tert-butyl α-hydroxyisobutyrate (533 mg, 3.32 mmol) in 4.5 mL DMF and 0.75 mL THF was added portion wise (133 mg, 3.32 mmol) sodium hydride at room temperature. After the reaction mixture had been stirring for 15 minutes, a solution of 2-(5-bromo-2-fluoro-phenyl)-2-difluoromethyl-1-(2-nitro-benzenesulfonyl)-aziridine (1 g, 2.22 mmol) was added. The reaction mixture was stirred at rt for 150 minutes and quenched with aqueous NH4Cl solution. TBME was added, the layers were separated, washed with brine and TBME. The combined organic layers were dried over MgSO4.H2O and evaporated. The crude product was purified on a silica gel column by eluting with hexane/EtOAc 6/1->5/1 to give 1.10 g of the title compound as a pale yellow resin. The reaction mixture was stirred at rt for 150 minutes quenched with aqueous NH4Cl solution TBME was added the layers were separated washed with brine and TBME The combined organic layers were dried over MgSO4.H2O evaporated The crude product was purified on a silica gel column by eluting with hexane/EtOAc 6/

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

Procedure: To a solution of tert-butyl α-hydroxyisobutyrate (533 mg, 3.32 mmol) in 4.5 mL DMF and 0.75 mL THF was added portion wise (133 mg, 3.32 mmol) sodium hydride at room temperature. After the reaction mixture had been stirring for 15 minutes, a solution of 2-(5-bromo-2-fluoro-phenyl)-2-difluoromethyl-1-(2-nitro-benzenesulfonyl)-aziridine (1 g, 2.22 mmol) was added. The reaction mixture was stirred at rt for 150 minutes and quenched with aqueous NH4Cl solution. TBME was added, the layers were separated, washed with brine and TBME. The combined organic layers were dried over MgSO4.H2O and evaporated. The crude product was purified on a silica gel column by eluting with hexane/EtOAc 6/1->5/1 to give 1.10 g of the title compound as a pale yellow resin. The reaction mixture was stirred at rt for 150 minutes quenched with aqueous NH4Cl solution TBME was added the layers were separated washed with brine and TBME The combined organic layers were dried over MgSO4.H2O evaporated The crude product was purified on a silica gel column by eluting with hexane/EtOAc 6/

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

Procedure: To a solution of tert-butyl α-hydroxyisobutyrate (533 mg, 3.32 mmol) in 4.5 mL DMF and 0.75 mL THF was added portion wise (133 mg, 3.32 mmol) sodium hydride at room temperature. After the reaction mixture had been stirring for 15 minutes, a solution of 2-(5-bromo-2-fluoro-phenyl)-2-difluoromethyl-1-(2-nitro-benzenesulfonyl)-aziridine (1 g, 2.22 mmol) was added. The reaction mixture was stirred at rt for 150 minutes and quenched with aqueous NH4Cl solution. TBME was added, the layers were separated, washed with brine and TBME. The combined organic layers were dried over MgSO4.H2O and evaporated. The crude product was purified on a silica gel column by eluting with hexane/EtOAc 6/1→5/1 to give 1.10 g of the title compound as a pale yellow resin. The reaction mixture was stirred at rt for 150 minutes quenched with aqueous NH4Cl solution TBME was added the layers were separated washed with brine and TBME The combined organic layers were dried over MgSO4.H2O evaporated The crude product was purified on a silica gel column by eluting with hexane/EtOAc 6/1→5/1

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

Procedure: With ice cooling, 72 mg of triphenylphosphine were dissolved in 1 ml of dry tetrahydrofuran, and 47 mg of diethyl azodicarboxylate were added. After 15 min, 80 mg of 4-[5-(2-fluorophenoxy)oxazolo[5,4-b]pyridin-2-yl]-2,6-dimethylphenol were added, followed by 32 μl of triethylamine and 44 mg of tert-butyl alpha-hydroxyisobutyrate. The reaction mixture was then stirred at room temperature for 16 hours, and another 72 mg of triphenylphosphine and 47 mg of diethyl azodicarboxylate were added with ice cooling. After a further 4 h at room temperature, the reaction was concentrated and purified by preparative HPLC. This gave 60 mg (53%) of the title compound. After a further 4 h at room temperature the reaction was concentrated purified by preparative HPLC

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

Procedure: To a solution of 388A (1.70 g, 7.35 mmol) and PPh3 (5.80 g, 22.1 mmol) in anhydrous THF (35 ml) was added t-butyl 2-hydroxyisobutyrate (3.83 ml, 22.1 mmol) followed by DEAD (3.47 ml, 22.1 mmol), the reaction mixture was stirred at rt for 19 h. More reagents PPh3 (1.16 g, 4.41 mmol), isobutyrate (0.77 ml, 4.41 mmol) and DEAD (0.69 ml, 4.41 mmol) were added, and the mixture was stirred for another 50 h, concentrated and purified by silica gel flash column chromatography to afford 388B (2.62 g, 96%) as a light pink crystalline solid (50%-80% CH2Cl2-hexanes). the mixture was stirred for another 50 h concentrated purified by silica gel flash column chromatography

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

Procedure: To a solution of tert-butyl α-hydroxyisobutyrate (533 mg, 3.32 mmol) in 4.5 mL DMF and 0.75 mL THF was added portion wise (133 mg, 3.32 mmol) sodium hydride at room temperature. After the reaction mixture had been stirring for 15 minutes, a solution of 2-(5-bromo-2-fluoro-phenyl)-2-difluoromethyl-1-(2-nitro-benzenesulfonyl)-aziridine (1 g, 2.22 mmol) was added. The reaction mixture was stirred at rt for 150 minutes and quenched with aqueous NH4Cl solution. TBME was added, the layers were separated, washed with brine and TBME. The combined organic layers were dried over MgSO4.H2O and evaporated. The crude product was purified on a silica gel column by eluting with hexane/EtOAc 6/1->5/1 to give 1.10 g of the title compound as a pale yellow resin. The reaction mixture was stirred at rt for 150 minutes quenched with aqueous NH4Cl solution TBME was added the layers were separated washed with brine and TBME The combined organic layers were dried over MgSO4.H2O evaporated The crude product was purified on a silica gel column by eluting with hexane/EtOAc 6/

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

Procedure: Bromoacetic acid (16.01 grams, 0.1 mole) is dissolved in tetra-hydrofuran (200 ml.) and 1,1-carbonyldiimidazole (16.22 grams, 0.1 mole) is added and the mixture stirred for an hour at 25° C. tert.-Butyl 2-hydroxy-2-methylpropanoate (10.41 grams, 0.1 mole) is added and the mixture stirred for 18 hours at 25° C. The solvent is removed by evaporation in vacuo to give tert. butyl 2-(2-bromoacetoxy)-2-methylpropanoate acid (0.1 mole). This compound is dissolved in ether, dried over anhydrous magnesium sulfate, filtered and the solvent removed by evaporation in vacuo. The product is dissolved in 1-propanol (100 ml.) and bis-(2-hydroxyethyl)amine (10.51 grams, 0.1 mole) and triethylamine (11.1 grams, 0.1 mole) are added and the mixture is stirred and heated at reflux for 3 hours. The volatile material is evaporated in vacuo, the residue dissolved in ether (250 ml.), washed with water and dried over anhydrous magnesium sulfate. The solvent is removed by evaporation in vacuo and dissolved in toluene (300 ml.). Methanesulfonic acid (2 grams) is added and the mixture refluxed for 2 hours. The mixture is cooled, extracted with water and the organic layer dried over anhydrous magnesium sulfate. The solvent is removed by evaporation in vacuo. The yield of 2-[N,N-bis-(2-hydroxyethyl)aminoacetoxy]-2-methylpropanoic acid is 17.45 g. (70%). is added The solvent is removed by evaporation in vacuo

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

Procedure: To a solution (22 mL) of tert-butyl 2-hydroxy-2-methylpropanoate (1.0 g) in N,N-dimethylformamide was added sodium hydride (250 mg) under an ice bath, and the mixture was stirred at room temperature for 1 hour. Thereafter, under an ice bath, 2-(3-bromopropoxy)tetrahydro-2H-pyran (0.88 mL) was added dropwise, and the mixture was stirred at room temperature overnight. To the reaction mixture were added water and 1N hydrochloric acid under an ice bath, followed by extraction with t-butyl methyl ether. The organic layer was sequentially washed with an aqueous saturated sodium bicarbonate solution and an aqueous saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:1) to obtain the title compound having the following physical property values, as a mixture (400 mg) with tert-butyl 2-hydroxy-2-methylpropanoate. the mixture was stirred at room temperature overnight followed by extraction with t-butyl methyl ether The organic layer was sequentially washed with an aqueous saturated sodium bicarbonate solution an aqueous saturated sodium chloride solution, dried with anhydrous sodium sulfate concentrated The residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:1)