3-[tert-butyl(dimethyl)silyl]oxypropanenitrile

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

Procedure: To a solution of 3-(tert-butyldimethylsilyloxy)propanenitrile (11.1 g, 60 mmol) in Et2O (400 mL) was added titanium tetraisopropanolate (28.9 g, 102 mmol) under N2 atmosphere. Ethylmagnesium bromide (3M in Et2O, 50 mL) was slowly added drop-wise at 0° C. The mixture was stirred at rt for 1 hr. Boron trifluoride etherate (17.0 g, 120 mmol) was slowly added at 0° C. The mixture was stirred at rt for 1 hr. The mixture was quenched with 10% aq. NaOH (300 mL) and then extracted with DCM (3×). The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (gradient elution 5-50% EtOAc/petroleum ether) to afford 1-(2-(tert-butyldimethylsilyloxy)ethyl)cyclopropanamine (3.9 g, 30%) as a colorless oil. ESI-MS (EI+, m/z): 216.2 [M+H]+. at 0° C The mixture was stirred at rt for 1 hr The mixture was quenched with 10% aq. NaOH (300 mL) extracted with DCM (3×) The combined organic layer was dried over Na2SO4 concentrated The residue was purified by silica gel column chromatography (gradient elution 5-50% EtOAc/petroleum ether)

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

Procedure: Imidazole (33.6 g, 495 mmol) and tert-butyldimethylsilyl chloride (27.2 g, 180 mmol) were added to a 0° C. solution of 3-hydroxypropanenitrile (10.6 g, 150 mmol) in DMF 50 mL). The mixture was allowed to warm to rt, then was stirred at rt for 12 hrs. The mixture was quenched with water (500 mL), and then extracted with EtOAc (3×). The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (gradient elution 0-5% EtOAc/petroleum ether) to give 3-(tert-butyldimethylsilyloxy)propanenitrile (18 g, 75%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 3.74 (t, J=6.0 Hz, 2H), 2.43 (t, J=6.0 Hz, 2H), 0.81 (s, 9H), 0.00 (s, 6H). The mixture was quenched with water (500 mL) extracted with EtOAc (3×) The combined organic layer was dried over Na2SO4 concentrated The residue was purified by silica gel column chromatography (gradient elution 0-5% EtOAc/petroleum ether)

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

Procedure: To a solution of 3-(tert-butyldimethylsilyloxy)propanenitrile (11.1 g, 60 mmol) in Et2O (400 mL) was added titanium tetraisopropanolate (28.9 g, 102 mmol) under N2 atmosphere. Ethylmagnesium bromide (3M in Et2O, 50 mL) was slowly added drop-wise at 0° C. The mixture was stirred at rt for 1 hr. Boron trifluoride etherate (17.0 g, 120 mmol) was slowly added at 0° C. The mixture was stirred at rt for 1 hr. The mixture was quenched with 10% aq. NaOH (300 mL) and then extracted with DCM (3×). The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (gradient elution 5˜50% EtOAc/petroleum ether) to afford 1-(2-(tert-butyldim ethylsilyloxy)ethyl)cyclopropanamine (3.9 g, 30%) as a colorless oil. ESI-MS (EI+, m/z): 216.2 [M+H]+. at 0° C The mixture was stirred at rt for 1 hr The mixture was quenched with 10% aq. NaOH (300 mL) extracted with DCM (3×) The combined organic layer was dried over Na2SO4 concentrated The residue was purified by silica gel column chromatography (gradient elution 5˜50% EtOAc/petroleum ether)

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

Procedure: Imidazole (33.6 g, 495 mmol) and tert-butyldimethylsilyl chloride (27.2 g, 180 mmol) were added to a 0° C. solution of 3-hydroxypropanenitrile (10.6 g, 150 mmol) in DMF 50 mL). The mixture was allowed to warm to rt, then was stirred at rt for 12 hrs. The mixture was quenched with water (500 mL), and then extracted with EtOAc (3×). The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (gradient elution 0˜5% EtOAc/petroleum ether) to give 3-(tert-butyldimethylsilyloxy) propanenitrile (18 g, 75%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 3.74 (t, J=6.0 Hz, 2H), 2.43 (t, J=6.0 Hz, 2H), 0.81 (s, 9H), 0.00 (s, 6H). The mixture was quenched with water (500 mL) extracted with EtOAc (3×) The combined organic layer was dried over Na2SO4 concentrated The residue was purified by silica gel column chromatography (gradient elution 0˜5% EtOAc/petroleum ether)

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

Procedure: To a solution of 3-(tert-butyldimethylsilyloxy)propanenitrile (11.1 g, 60 mmol) in Et2O (400 mL) was added titanium tetraisopropanolate (28.9 g, 102 mmol) under N2 atmosphere. Ethylmagnesium bromide (3M in Et2O, 50 mL) was slowly added drop-wise at 0° C. The mixture was stirred at rt for 1 hr. Boron trifluoride etherate (17.0 g, 120 mmol) was slowly added at 0° C. The mixture was stirred at rt for 1 hr. The mixture was quenched with 10% aq. NaOH (300 mL) and then extracted with DCM (3×). The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (gradient elution 5˜50% EtOAc/petroleum ether) to afford 1-(2-(tert-butyldim ethylsilyloxy)ethyl)cyclopropanamine (3.9 g, 30%) as a colorless oil. ESI-MS (EI+, m/z): 216.2 [M+H]+. at 0° C The mixture was stirred at rt for 1 hr The mixture was quenched with 10% aq. NaOH (300 mL) extracted with DCM (3×) The combined organic layer was dried over Na2SO4 concentrated The residue was purified by silica gel column chromatography (gradient elution 5˜50% EtOAc/petroleum ether)

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

Procedure: Imidazole (33.6 g, 495 mmol) and tert-butyldimethylsilyl chloride (27.2 g, 180 mmol) were added to a 0° C. solution of 3-hydroxypropanenitrile (10.6 g, 150 mmol) in DMF 50 mL). The mixture was allowed to warm to rt, then was stirred at rt for 12 hrs. The mixture was quenched with water (500 mL), and then extracted with EtOAc (3×). The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (gradient elution 0˜5% EtOAc/petroleum ether) to give 3-(tert-butyldimethylsilyloxy) propanenitrile (18 g, 75%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 3.74 (t, J=6.0 Hz, 2H), 2.43 (t, J=6.0 Hz, 2H), 0.81 (s, 9H), 0.00 (s, 6H). The mixture was quenched with water (500 mL) extracted with EtOAc (3×) The combined organic layer was dried over Na2SO4 concentrated The residue was purified by silica gel column chromatography (gradient elution 0˜5% EtOAc/petroleum ether)

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

Procedure: To a solution of 3-(tert-butyldimethylsilyloxy)propanenitrile (11.1 g, 60 mmol) in Et2O (400 mL) was added titanium tetraisopropanolate (28.9 g, 102 mmol) under N2 atmosphere. Ethylmagnesium bromide (3M in Et2O, 50 mL) was slowly added drop-wise at 0° C. The mixture was stirred at rt for 1 hr. Boron trifluoride etherate (17.0 g, 120 mmol) was slowly added at 0° C. The mixture was stirred at rt for 1 hr. The mixture was quenched with 10% aq. NaOH (300 mL) and then extracted with DCM (3×). The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (gradient elution 5˜50% EtOAc/petroleum ether) to afford 1-(2-(tert-butyldimethylsilyloxy)ethyl)cyclopropanamine (3.9 g, 30%) as a colorless oil. ESI-MS (EI+, m/z): 216.2 [M+H]+. at 0° C The mixture was stirred at rt for 1 hr The mixture was quenched with 10% aq. NaOH (300 mL) extracted with DCM (3×) The combined organic layer was dried over Na2SO4 concentrated The residue was purified by silica gel column chromatography (gradient elution 5˜50% EtOAc/petroleum ether)

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

Procedure: Imidazole (33.6 g, 495 mmol) and tert-butyldimethylsilyl chloride (27.2 g, 180 mmol) were added to a 0° C. solution of 3-hydroxypropanenitrile (10.6 g, 150 mmol) in DMF 50 mL). The mixture was allowed to warm to rt, then was stirred at rt for 12 hrs. The mixture was quenched with water (500 mL), and then extracted with EtOAc (3×). The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (gradient elution 0-5% EtOAc/petroleum ether) to give 3-(tert-butyldimethylsilyloxy) propanenitrile (18 g, 75%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 3.74 (t, J=6.0 Hz, 2H), 2.43 (t, J=6.0 Hz, 2H), 0.81 (s, 9H), 0.00 (s, 6H). The mixture was quenched with water (500 mL) extracted with EtOAc (3×) The combined organic layer was dried over Na2SO4 concentrated The residue was purified by silica gel column chromatography (gradient elution 0-5% EtOAc/petroleum ether)

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

Procedure: To a solution of 3-(tert-butyldimethylsilyloxy)propanenitrile (11.1 g, 60 mmol) in Et2O (400 mL) was added titanium tetraisopropanolate (28.9 g, 102 mmol) under N2 atmosphere. Ethylmagnesium bromide (3-M in Et2O, 50 mL) was slowly added drop-wise at 0° C. The mixture was stirred at rt for 1 hr. Boron trifluoride etherate (17.0 g, 120 mmol) was slowly added at 0° C. The mixture was stirred at rt for 1 hr. The mixture was quenched with 10% aq. NaOH (300 mL) and then extracted with DCM (3×). The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (gradient elution 5-50% EtOAc/petroleum ether) to afford 1-(2-(tert-butyldim ethylsilyloxy)ethyl)cyclopropanamine (3.9 g, 30%) as a colorless oil. ESI-MS (EI+, m/z): 216.2 [M+H]+. at 0° C The mixture was stirred at rt for 1 hr The mixture was quenched with 10% aq. NaOH (300 mL) extracted with DCM (3×) The combined organic layer was dried over Na2SO4 concentrated The residue was purified by silica gel column chromatography (gradient elution 5-50% EtOAc/petroleum ether)

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

Procedure: Imidazole (33.6 g, 495 mmol) and tert-butyldimethylsilyl chloride (27.2 g, 180 mmol) were added to a 0° C. solution of 3-hydroxypropanenitrile (10.6 g, 150 mmol) in DMF 50 mL). The mixture was allowed to warm to rt, then was stirred at rt for 12 hrs. The mixture was quenched with water (500 mL), and then extracted with EtOAc (3×). The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (gradient elution 0-5% EtOAc/petroleum ether) to give 3-(tert-butyldimethylsilyloxy) propanenitrile (18 g, 75%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 3.74 (t, J=6.0 Hz, 2H), 2.43 (t, J=6.0 Hz, 2H), 0.81 (s, 9H), 0.00 (s, 6H). The mixture was quenched with water (500 mL) extracted with EtOAc (3×) The combined organic layer was dried over Na2SO4 concentrated The residue was purified by silica gel column chromatography (gradient elution 0-5% EtOAc/petroleum ether)