tert-butyl N-[(2R)-1-hydroxy-3-methylbutan-2-yl]carbamate

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

Procedure: The title compound has been prepared in 67% yield from the alcohol of Example 6, Step B and methyl iodide following the alkylation method given in Example 6, Step C.

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

Procedure: To a solution of N-tert-butoxycarbonyl-D-valinol (10 g, 49.3 mmol) and benzylbromide (5.86 ml, 49.3 mmol) in anhydrous dimethyl formamide (50 ml) was added at -5° C. and under nitrogen, potassium-tert-butoxide (11.06 g, 98.6 mmol) as a solid, portionwise, an in such a way that the internal temperature does not exceed +5° C. The reaction mixture was stirred for 2 hours at 0° C., diluted with ethyl acetate (2×300 ml), extracted with a 1N solution of potassium hydrogenosulfate (50 ml) and water (250 ml) and washed twice with water (2×200 ml). After drying of the organic phase on sodium sulfate, filtration and concentration in vacuo, the resulting oil was purified by flash chromatography (silica gel, ethyl acetate/petroleum ether: 1/9, Rf: 0.42) to give the title compound as a colorless oil (9.95 g, 69% yield). does not exceed +5° C extracted with a 1N solution of potassium hydrogenosulfate (50 ml) and water (250 ml) washed twice with water (2×200 ml) After drying of the organic phase on sodium sulfate, filtration and concentration in vacuo the resulting oil was purified by flash chromatography (silica gel, ethyl acetate/petroleum ether: 1/9, Rf: 0.42)

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

Procedure: To a solution of N-tert-butoxycarbonyl-(D)-valinol (10 g, 49.3 mmol) and benzylbromide (5.86 ml, 49.3 mmol) in anhydrous DMF (50 ml) was added at -5° C. and under nitrogen, potassium-tert-butoxide (11.06 g, 98.6 mmol) as a solid, portionwise, and in such a way that the internal temperature does not exceed +5° C. The reaction mixture was stirred for 2 hours at 0° C., diluted with ethyl acetate (2×300 ml), extracted with a 1N solution of potassium hydrogenosulfate (50 ml) and water (250 ml) and washed twice with water (2×200 ml). After drying of the organic phase on sodium sulfate, filtration and concentration in vacuo, the resulting oil was purified by flash chromatography (silica gel, ethyl acetate/petroleum ether: 1/9, Rf.: 0.42) to give the title compound as a colorless oil (9.95 g, 69% yield). does not exceed +5° C extracted with a 1N solution of potassium hydrogenosulfate (50 ml) and water (250 ml) washed twice with water (2×200 ml) After drying of the organic phase on sodium sulfate, filtration and concentration in vacuo the resulting oil was purified by flash chromatography (silica gel, ethyl acetate/petroleum ether: 1/9, Rf.: 0.42)

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

Procedure: The title compound has been prepared in 67% yield from the alcohol of Example 6, Step B and methyl iodide following the alkylation method given in Example 6, Step C. Rf: 0.27 (silica gel, ethyl acetate/petroleum ether: 1/9).

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

Procedure: The title compound has been prepared in 67% yield from the alcohol of Example 6, Step B and methyl iodide following the alkylation method given in Example 6, Step C. Rf: 0.27 (silica gel, ethyl acetate/petroleum ether: 1/9).

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

Procedure: To a solution of N-tert-butoxycarbonyl-D-valinol (10 g, 49.3 mmol) and benzylbromide (5.86 ml, 49.3 mmol) in anhydrous dimethyl formamide (50 ml) was added at -5° C. and under nitrogen, potassium-tert-butoxide (11.06 g, 98.6 mmol) as a solid, portionwise, an in such a way that the internal temperature does not exceed +5° C. The reaction mixture was stirred for 2 hours at 0° C., diluted with ethyl acetate (2×300 ml), extracted with a 1N solution of potassium hydrogenosulfate (50 ml) and water (250 ml) and washed twice with water (2×200 ml). After drying of the organic phase on sodium sulfate, filtration and concentration in vacuo, the resulting oil was purified by flash chromatography (silica gel, ethyl acetate/petroleum ether: 1/9, Rf: 0.42) to give the title compound as a colorless oil (9.95 g, 69% yield). MS: [MH]+ =294. does not exceed +5° C extracted with a 1N solution of potassium hydrogenosulfate (50 ml) and water (250 ml) washed twice with water (2×200 ml) After drying of the organic phase on sodium sulfate, filtration and concentration in vacuo the resulting oil was purified by flash chromatography (silica gel, ethyl acetate/petroleum ether: 1/9, Rf: 0.42)

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

Procedure: To a solution of N-tert-butoxycarbonyl-D-valinol (10 g, 49.3 mmol) and benzylbromide (5.86 ml, 49.3 mmol) in anhydrous dimethyl formamide (50 ml) was added at -5° C. and under nitrogen, potassium-tert-butoxide (11.06 g, 98.6 mmol) as a solid, portionwise, an in such a way that the internal temperature does not exceed +5° C. The reaction mixture was stirred for 2 hours at 0° C., diluted with ethyl acetate (2×300 ml), extracted with a 1N solution of potassium hydrogenosulfate (50 ml) and water (250 ml) and washed twice with water (2×200 ml). After drying of the organic phase on sodium sulfate, filtration and concentration in vacuo, the resulting oil was purified by flash chromatography (silica gel, ethyl acetate/petroleum ether: 1/9, Rf: 0.42) to give the title compound as a colorless oil (9.95 g, 69% yield). MS: [MH]+ =294. does not exceed +5° C extracted with a 1N solution of potassium hydrogenosulfate (50 ml) and water (250 ml) washed twice with water (2×200 ml) After drying of the organic phase on sodium sulfate, filtration and concentration in vacuo the resulting oil was purified by flash chromatography (silica gel, ethyl acetate/petroleum ether: 1/9, Rf: 0.42)

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

Procedure: The title compound has been prepared in 67% yield from the alcohol of Example 6, Step B and methyl iodide following the alkylation method given in Example 6, Step C.

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

Procedure: To a solution of N-tert-butoxycarbonyl-D-valinol (10 g, 49.3 mmol) and benzylbromide (5.86 ml, 49.3 mmol) in anhydrous dimethyl formamide (50 ml) was added at -5° C. and under nitrogen, potassium-tert-butoxide (11.06 g, 98.6 mmol) as a solid, portionwise, an in such a way that the internal temperature does not exceed +5° C. The reaction mixture was stirred for 2 hours at 0° C., diluted with ethyl acetate (2×300 ml), extracted with a 1N solution of potassium hydrogenosulfate (50 ml) and water (250 ml) and washed twice with water (2×200 ml). After drying of the organic phase on sodium sulfate, filtration and concentration in vacuo, the resulting oil was purified by flash chromatography (silica gel, ethyl acetate/petroleum ether: 1/9, Rf: 0.42) to give the title compound as a colorless oil (9.95 g, 69% yield). does not exceed +5° C extracted with a 1N solution of potassium hydrogenosulfate (50 ml) and water (250 ml) washed twice with water (2×200 ml) After drying of the organic phase on sodium sulfate, filtration and concentration in vacuo the resulting oil was purified by flash chromatography (silica gel, ethyl acetate/petroleum ether: 1/9, Rf: 0.42)

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

Procedure: To a solution of N-tert-butoxycarbonyl-D-valinol (10 g, 49.3 mmol) and benzylbromide (5.86 ml, 49.3 mmol) in anhydrous dimethyl formamide (50 ml) was added at -5° C. and under nitrogen, potassium-tert-butoxide (11.06 g, 98.6 mmol) as a solid, portionwise, an in such a way that the internal temperature does not exceed +5° C. The reaction mixture was stirred for 2 hours at 0° C., diluted with ethyl acetate (2×300 ml), extracted with a 1N solution of potassium hydrogenosulfate (50 ml) and water (250 ml) and washed twice with water (2×200 ml). After drying of the organic phase on sodium sulfate, filtration and concentration in vacuo, the resulting oil was purified by flash chromatography (silica gel, ethyl acetate/petroleum ether: 1/9, Rf: 0.42) to give the title compound as a colorless oil (9.95 g, 69% yield). does not exceed +5° C extracted with a 1N solution of potassium hydrogenosulfate (50 ml) and water (250 ml) washed twice with water (2×200 ml) After drying of the organic phase on sodium sulfate, filtration and concentration in vacuo the resulting oil was purified by flash chromatography (silica gel, ethyl acetate/petroleum ether: 1/9, Rf: 0.42)

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

Procedure: To a solution of N-tert-butoxycarbonyl-(D)-valinol (10 g, 49.3 mmol) and benzylbromide (5.86 ml, 49.3 mmol) in anhydrous DMF (50 ml) was added at -5° C. and under nitrogen, potassium-tert-butoxide (11.06 g, 98.6 mmol) as a solid, portionwise, and in such a way that the internal temperature does not exceed +5° C. The reaction mixture was stirred for 2 hours at 0° C., diluted with ethyl acetate (2×300 ml), extracted with a 1N solution of potassium hydrogenosulfate (50 ml) and water (250 ml) and washed twice with water (2×200 ml). After drying of the organic phase on sodium sulfate, filtration and concentration in vacuo, the resulting oil was purified by flash chromatography (silica gel, ethyl acetate/petroleum ether: 1/9, Rf.: 0.42) to give the title compound as a colorless oil (9.95 g, 69% yield). MS: MH+ =294. does not exceed +5° C extracted with a 1N solution of potassium hydrogenosulfate (50 ml) and water (250 ml) washed twice with water (2×200 ml) After drying of the organic phase on sodium sulfate, filtration and concentration in vacuo the resulting oil was purified by flash chromatography (silica gel, ethyl acetate/petroleum ether: 1/9, Rf.: 0.42)

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

Procedure: To a solution of N-tert-butoxycarbonyl-D-valinol (10 g, 49.3 mmol) and benzylbromide (5.86 mL, 49.3 mmol) in anhydrous dimethyl formamide (50 mL) is added at -5° C. and under nitrogen, potassium-tert-butoxide (11.06 g, 98.6 mmol) as a solid, portionwise, an in such a way that the internal temperature does not exceed +5° C. The reaction mixture is stirred for 2 hours at 0° C., diluted with ethyl acetate (2×300 mL), extracted with a 1N solution of potassium hydrogen sulfate (50 mL) and water (250 mL) and is washed twice with water (2×200 mL). After drying of the organic phase over anhydrous sodium sulfate, filtration and concentration under vacuum, the oil is purified by flash chromatography (silica gel, ethyl acetate/petroleum ether: 1/9, Rf: 0.42) to provide N-tert-butoxycarbonyl-O-benzyl-D-valinol as a colorless oil (9.95 g, 69% yield). does not exceed +5° C extracted with a 1N solution of potassium hydrogen sulfate (50 mL) and water (250 mL) is washed twice with water (2×200 mL) After drying of the organic phase over anhydrous sodium sulfate, filtration and concentration under vacuum the oil is purified by flash chromatography (silica gel, ethyl acetate/petroleum ether: 1/9, Rf: 0.42)