3-hydroxy-3-methylbutan-2-one

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 stirred solution of 3-methyl-3-hydroxy-2-butanone (40 g, 0.392 mol) in anhydrous dichloromethane (2.2 l) under nitrogen was added solid pyridinium tribromide (250.4 g, 0.784 mol) in portions and the mixture was stirred at room temperature for 14 h. The mixture was then washed with dilute aqueous sodium hydrogensulphite (500 ml), then saturated aqueous NaCl (500 ml), dried (Na2SO4), and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, CH2Cl2) to afford 31.4 g (31%) of the title compound as a colourless oil: 1H NMR (360 MHz, CDCl3) δ 1.54 (6H, s), 2.45 (1H, br s), 6.62 (1H, s). The mixture was then washed with dilute aqueous sodium hydrogensulphite (500 ml) saturated aqueous NaCl (500 ml), dried (Na2SO4) evaporated in vacuo The residue was purified by flash chromatography (silica gel, CH2Cl2)

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 of TFA-Phe-Leu-OMe (0.56 mmol) in MeOH was added N-methylmorpholine (0.93 mL, pH=7), 3-hydroxy-3-methyl-2-butanone (0.84 mmol), and NaCNBH3 (0.72 mmol) under a N2 atmosphere. The reaction mixture was stirred overnight at room temperature and quenched with 50 mL of saturated NaHCO3. The aqueous layer was extracted 3 times with EtOAc (25 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, concentrated, and then flash chromatographed (1-3% MeOH/CH2Cl2 ; SiO2 gel) to yield 0.17 g (80% yield) of N-(2-hydroxy-2-methyl-1-methylpropyl)-L-phenylalanyl-L-leucine methyl ester as an oil. quenched with 50 mL of saturated NaHCO3 The aqueous layer was extracted 3 times with EtOAc (25 mL) The combined organic layers were washed with brine dried over MgSO4 filtered concentrated flash chromatographed (1-3% MeOH/CH2Cl2 ; SiO2 gel)

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of sodium tert-butoxide (12 g, 125 mmol), XANTPHOS (2.05 g, 3.5 mmol) and Pd2(dba)3 (1.35 g, 1.5 mmol) in THF (600 mL) was added 4-bromothioanisole (20 g, 98 mmol) and 3-hydroxy-3-methyl-butan-2-one (12 g, 117 mmol). The resulting reaction mixture was heated to 75° C. for 2 h then cooled to r.t. and diluted with water. The organic extracts were washed (H2O), (brine), dried (MgSO4), filtered and concentrated. Purification by flash chromatography (eluting with hexane/ethyl acetate, 85:15-80:20) provided the title compound as a pale brown solid. The resulting reaction mixture then cooled to r.t. The organic extracts were washed (H2O), (brine), dried (MgSO4) filtered concentrated Purification by flash chromatography (eluting with hexane/ethyl acetate, 85:15-80:20)

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of sodium tert-butoxide (12 g, 125 mmol), XANTPHOS (2.05 g, 3.5 mmol) and Pd2(dba)3 (1.35 g, 1.5 mmol) in THF (600 mL) was added 4-bromothioanisole (20 g, 98 mmol) and 3-hydroxy-3-methyl-butan-2-one (12 g, 117 mmol). The resulting reaction mixture was heated to 75° C. for 2 h then cooled to r.t. and diluted with water. The organic extracts were washed (H2O), (brine), dried (MgSO4), filtered and concentrated. Purification by flash chromatography (eluting with hexane/ethyl acetate, 85:15-80:20) provided the title compound as a pale brown solid. The resulting reaction mixture then cooled to r.t. The organic extracts were washed (H2O), (brine), dried (MgSO4) filtered concentrated Purification by flash chromatography (eluting with hexane/ethyl acetate, 85:15-80:20)

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

Procedure: To a stirred solution of 3-methyl-3-hydroxy-2-butanone (40 g, 0.392 mol) in anhydrous dichloromethane (2.2 l) under nitrogen was added solid pyridinium tribromide (250.4 g, 0.784 mol) in portions and the mixture was stirred at room temperature for 14 h. The mixture was then washed with dilute aqueous sodium hydrogensulphite (500 ml), then saturated aqueous NaCl (500 ml), dried (Na2SO4), and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, CH2Cl2) to afford 31.4 g (31%) of the title compound as a colourless oil: 1H NMR (360 MHz, CDCl3) δ 1.54 (6H, s), 2.45 (1H, br s), 6.62 (1H, s). The mixture was then washed with dilute aqueous sodium hydrogensulphite (500 ml) saturated aqueous NaCl (500 ml), dried (Na2SO4) evaporated in vacuo The residue was purified by flash chromatography (silica gel, CH2Cl2)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1,3-dibromobenzene (1.0 eq.), 3-hydroxy-3-methyl-butan-2-one (1.0 eq.), Pd2(dba)3 (0.02 eq.), xantphos (0.04 eq.) and t-BuONa (1.1 eq.) in THF (0.15M) was stirred at 60° C. for 2 h, poured in saturated aqueous NH4Cl and extracted with EtOAc (2×). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. Flash chromatography (Hex:EtOAc; 7:3) afforded the title compound as an oil. extracted with EtOAc (2×) The combined organic extracts were washed with brine dried over Na2SO4 filtered concentrated

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

Procedure: To a stirred solution of 3-methyl-3-hydroxy-2-butanone (40 g, 0.392 mol) in anhydrous dichloromethane (2.2 l) under nitrogen was added solid pyridinium tribromide (250.4 g, 0.784 mol) in portions and the mixture was stirred at room temperature for 14 h. The mixture was then washed with dilute aqueous sodium hydrogensulfite (500 ml), then saturated aqueous NaCl (500 ml), dried (Na2SO4), and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, CH2Cl2) to afford 31.4 g (31%) of the title compound as a colourless oil: 1H NMR (360 MHz, CDCl3) δ 1.54 (6H, s), 2.45 (1H, br s), 6.62 (1H, s). The mixture was then washed with dilute aqueous sodium hydrogensulfite (500 ml) saturated aqueous NaCl (500 ml), dried (Na2SO4) evaporated in vacuo The residue was purified by flash chromatography (silica gel, CH2Cl2)

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

Procedure: To a stirred solution of 3-methyl-3-hydroxy-2-butanone (40 g, 0.392 mol) in anhydrous dichloromethane (2.2 l) under nitrogen was added solid pyridinium tribromide (250.4 g, 0.784 mol) in portions and the mixture was stirred at room temperature for 14 h. The mixture was then washed with dilute aqueous sodium hydrogensulphite (500 ml), then saturated aqueous NaCl (500 ml), dried (Na2SO4), and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, CH2Cl2) to afford 31.4 g (31%) of the title compound as a colourless oil: 1H NMR (360 MHz, CDCl3) δ 1.54 (6H, s), 2.45 (1H, br s), 6.62 (1H, s). The mixture was then washed with dilute aqueous sodium hydrogensulphite (500 ml) saturated aqueous NaCl (500 ml), dried (Na2SO4) evaporated in vacuo The residue was purified by flash chromatography (silica gel, CH2Cl2)

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

Procedure: To a stirred solution of 3-methyl-3-hydroxy-2-butanone (40 g, 0.392 mol) in anhydrous dichloromethane (2.2 l) under nitrogen was added solid pyridinium tribromide (250.4 g, 0.784 mol) in portions and the mixture was stirred at room temperature for 14 h. The mixture was then washed with dilute aqueous sodium hydrogensulphite (500 ml), then saturated aqueous NaCl (500 ml), dried (Na2SO4), and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, CH2Cl2) to afford 31.4 g (31%) of the title compound as a colourless oil: 1H NMR (360 MHz, CDCl3) δ 1.54 (6H, s), 2.45 (1H, br s), 6.62 (1H, s). The mixture was then washed with dilute aqueous sodium hydrogensulphite (500 ml) saturated aqueous NaCl (500 ml), dried (Na2SO4) evaporated in vacuo The residue was purified by flash chromatography (silica gel, CH2Cl2)