tert-butyl-dimethyl-[[(2R)-oxiran-2-yl]methoxy]silane

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: tert-BuLi (12.4 ml, 1.7M, 21.1 mmol) was added to a solution of TMS-acetylene (2.12 g, 21.7 mmol) in THF (40 ml) at −78° C. and the reaction mixture was stirred for an additional 30 min. (R)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane (2 g, 10.6 mmol) and BF3.EtO2 (3 g, 21.1 mmol) were added and stirred at −78° C. for 4.5 hours. The reaction was then quenched by addition of aqueous ammonium chloride solution and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure to afford the desired material in a quantitative yield. The material was used in the next step with no further purification. EtO2 (3 g, 21.1 mmol) were added The reaction was then quenched by addition of aqueous ammonium chloride solution the mixture was extracted with ethyl acetate (3×50 mL) The combined organic layers were washed with brine dried (MgSO4) concentrated under reduced pressure

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: tert-Butyl-chloro-dimethylsilane (12.9 g, 85.5 mmol) followed by Et3N (19 mL, 136 mmol) was added to a 0° C. solution of (S)-(+)-glycidol (5.0 g, 67 mmol) in CH2Cl2 (200 mL). The solution was allowed to warm to 23° C. with stirring over 17 h. The resulting pink solution was diluted with Et2O (800 mL) and stirred an additional 30 min. The Et2O layer was washed with saturated aqueous NaHCO3 (200 mL), H2O (2×100 mL), brine (100 mL), dried over Na2SO4 and concentrated. Purification by column chromatography (silica, 5-10% Et2O/hexanes) gave (R)-tert-Butyl-dimethyl-oxiranylmethoxy-silane (10.01 g, 79%). TLC (silica, 10% Et2O/hexanes): Rf=0.5. 1H NMR (CDCl3, 400 MHz): 3.85 (dd, J=11.9, 3.2 Hz, 1H), 3.66 (dd, J=11.9, 4.8 Hz, 1H), 3.09 (m, 1H), 2.77 (dd, J=5.0, 4.2 Hz, 1H), 2.64 (dd, J=5.2, 2.7 Hz, 1H), 0.90 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H). stirred an additional 30 min The Et2O layer was washed with saturated aqueous NaHCO3 (200 mL), H2O (2×100 mL), brine (100 mL) dried over Na2SO4 concentrated Purification by column chromatography (silica, 5-10% Et2O/hexanes)

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: tert-Butyl-chloro-dimethylsilane (12.9 g, 85.5 mmol) followed by Et3N (19 mL, 136 mmol) was added to a 0° C. solution of (S)-(+)-glycidol (5.0 g, 67 mmol) in CH2Cl2 (200 mL). The solution was allowed to warm to 23° C. with stirring over 17 h. The resulting pink solution was diluted with Et2O (800 mL) and stirred an additional 30 min. The Et2O layer was washed with saturated aqueous NaHCO3 (200 mL), H2O (2×100 mL), brine (100 mL), dried over Na2SO4 and concentrated. Purification by column chromatography (silica, 5-10% Et2O/hexanes) gave (R)-tert-Butyl-dimethyl-oxiranylmethoxy-silane (10.01 g, 79%). TLC (silica, 10% Et2O/hexanes): Rf=0.5. 1H NMR (CDCl3, 400 MHz): 3.85 (dd, J=11.9, 3.2 Hz, 1H), 3.66 (dd, J=11.9, 4.8 Hz, 1H), 3.09 (m, 1H), 2.77 (dd, J=5.0, 4.2 Hz, 1H), 2.64 (dd, J=5.2, 2.7 Hz, 1H), 0.90 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H). stirred an additional 30 min The Et2O layer was washed with saturated aqueous NaHCO3 (200 mL), H2O (2×100 mL), brine (100 mL) dried over Na2SO4 concentrated Purification by column chromatography (silica, 5-10% Et2O/hexanes)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: tert-BuLi (12.4 ml, 1.7M, 21.1 mmol) was added to a solution of TMS-acetylene (2.12 g, 21.7 mmol) in THF (40 ml) at −78° C. and the reaction mixture was stirred for an additional 30 min. (R)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane (2 g, 10.6 mmol) and BF3.EtO2 (3 g, 21.1 mmol) were added and stirred at −78° C. for 4.5 hours. The reaction was then quenched by addition of aqueous ammonium chloride solution and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure to afford the desired material in a quantitative yield. The material was used in the next step with no further purification. EtO2 (3 g, 21.1 mmol) were added The reaction was then quenched by addition of aqueous ammonium chloride solution the mixture was extracted with ethyl acetate (3×50 mL) The combined organic layers were washed with brine dried (MgSO4) concentrated under reduced pressure

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: tert-BuLi (12.4 ml, 1.7M, 21.1 mmol) was added to a solution of TMS-acetylene (2.12 g, 21.7 mmol) in THF (40 ml) at −78° C. and the reaction mixture was stirred for an additional 30 min. (R)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane (2 g, 10.6 mmol) and BF3.EtO2 (3 g, 21.1 mmol) were added and stirred at −78° C. for 4.5 hours. The reaction was then quenched by addition of aqueous ammonium chloride solution and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure to afford the desired material in a quantitative yield. The material was used in the next step with no further purification. EtO2 (3 g, 21.1 mmol) were added The reaction was then quenched by addition of aqueous ammonium chloride solution the mixture was extracted with ethyl acetate (3×50 mL) The combined organic layers were washed with brine dried (MgSO4) concentrated under reduced pressure

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

Procedure: n-Butyllithium (58.2 mL, 2.64 M solution in hexane) was added dropwise to a suspension of trimethylsulfonium iodide (32.4 g) in tetrahydrofuran (400 mL) in a nitrogen atmosphere at −20° C. The reaction solution was stirred at the same temperature for 30 minutes. tert-Butyldimethylsilyl (R)-(−)-glycidyl ether (10 g) was added dropwise to the reaction solution at the same temperature. The reaction solution was stirred for three hours with gradual heating to room temperature. Aqueous ammonium chloride and ethyl acetate were added to the reaction solution, and the organic layer was separated. The organic layer was washed with saturated aqueous sodium chloride twice. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (9.6 g). The reaction solution was stirred for three hours the organic layer was separated The organic layer was washed with saturated aqueous sodium chloride twice The organic layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography

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

Procedure: n-Butyllithium (58.2 mL, 2.64 M solution in hexane) was added dropwise to a suspension of trimethylsulfonium iodide (32.4 g) in tetrahydrofuran (400 mL) in a nitrogen atmosphere at −20° C. The reaction solution was stirred at the same temperature for 30 minutes. tert-Butyldimethylsilyl (R)-(−)-glycidyl ether (10 g) was added dropwise to the reaction solution at the same temperature. The reaction solution was stirred for three hours with gradual heating to room temperature. Aqueous ammonium chloride and ethyl acetate were added to the reaction solution, and the organic layer was separated. The organic layer was washed with saturated aqueous sodium chloride twice. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (9.6 g). The reaction solution was stirred for three hours the organic layer was separated The organic layer was washed with saturated aqueous sodium chloride twice The organic layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: tert-BuLi (12.4 ml, 1.7M, 21.1 mmol) was added to a solution of TMS-acetylene (2.12 g, 21.7 mmol) in THF (40 ml) at −78° C. and the reaction mixture was stirred for an additional 30 min. (R)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane (2 g, 10.6 mmol) and BF3.EtO2 (3 g, 21.1 mmol) were added and stirred at −78° C. for 4.5 hours. The reaction was then quenched by addition of aqueous ammonium chloride solution and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure to afford the desired material in a quantitative yield. The material was used in the next step with no further purification. EtO2 (3 g, 21.1 mmol) were added The reaction was then quenched by addition of aqueous ammonium chloride solution the mixture was extracted with ethyl acetate (3×50 mL) The combined organic layers were washed with brine dried (MgSO4) concentrated under reduced pressure

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: tert-Butyl-chloro-dimethylsilane (12.9 g, 85.5 mmol) followed by Et3N (19 mL, 136 mmol) was added to a 0° C. solution of (S)-(+)-glycidol (5.0 g, 67 mmol) in CH2Cl2 (200 mL). The solution was allowed to warm to 23° C. with stirring over 17 h. The resulting pink solution was diluted with Et2O (800 mL) and stirred an additional 30 min. The Et2O layer was washed with saturated aqueous NaHCO3 (200 mL), H2O (2×100 mL), brine (100 mL), dried over Na2SO4 and concentrated. Purification by column chromatography (silica, 5-10% Et2O/hexanes) gave (R)-tert-Butyl-dimethyl-oxiranylmethoxy-silane (10.01 g, 79%). TLC (silica, 10% Et2O/hexanes): Rf=0.5. 1H NMR (CDCl3, 400 MHz): 3.85 (dd, J=11.9, 3.2 Hz, 1H), 3.66 (dd, J=11.9, 4.8 Hz, 1H), 3.09 (m, 1H), 2.77 (dd, J=5.0, 4.2 Hz, 1H), 2.64 (dd, J=5.2, 2.7 Hz, 1H), 0.90 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H). stirred an additional 30 min The Et2O layer was washed with saturated aqueous NaHCO3 (200 mL), H2O (2×100 mL), brine (100 mL) dried over Na2SO4 concentrated Purification by column chromatography (silica, 5-10% Et2O/hexanes)

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

Procedure: A solution of (S)-glycidol (2.5 g, 33.7 mmol) in 100 mL of 1:1 DCM/DMF was cooled to 0° C. and treated with TBDMS-Cl (6.10 g, 40.5 mmol) and imidazole (3.45 g, 50.6 mmol). The mixture was stirred overnight at 0° C. Solution was diluted with DCM and washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4 and concentrated to provide A-1 as a colorless oil. Data for A-1: LRMS m/z (M+H)=189.21 found; 189.34 required washed with saturated aqueous NaHCO3 and brine dried over Na2SO4 concentrated to provide A-1 as a colorless oil

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: tert-Butyl-chloro-dimethylsilane (12.9 g, 85.5 mmol) followed by Et3N (19 mL, 136 mmol) was added to a 0° C. solution of (S)-(+)-glycidol (5.0 g, 67 mmol) in CH2Cl2 (200 mL). The solution was allowed to warm to 23° C. with stirring over 17 h. The resulting pink solution was diluted with Et2O (800 mL) and stirred an additional 30 min. The Et2O layer was washed with saturated aqueous NaHCO3 (200 mL), H2O (2×100 mL), brine (100 mL), dried over Na2SO4 and concentrated. Purification by column chromatography (silica, 5-10% Et2O/hexanes) gave (R)-tert-Butyl-dimethyl-oxiranylmethoxy-silane (10.01 g, 79%). TLC (silica, 10% Et2O/hexanes): Rf=0.5. 1H NMR (CDCl3, 400 MHz): 3.85 (dd, J=11.9, 3.2 Hz, 1H), 3.66 (dd, J=11.9, 4.8 Hz, 1H), 3.09 (m, 1H), 2.77 (dd, J=5.0, 4.2 Hz, 1H), 2.64 (dd, J=5.2, 2.7 Hz, 1H), 0.90 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H). stirred an additional 30 min The Et2O layer was washed with saturated aqueous NaHCO3 (200 mL), H2O (2×100 mL), brine (100 mL) dried over Na2SO4 concentrated Purification by column chromatography (silica, 5-10% Et2O/hexanes)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: tert-BuLi (12.4 ml, 1.7M, 21.1 mmol) was added to a solution of TMS-acetylene (2.12 g, 21.7 mmol) in THF (40 ml) at −78° C. and the reaction mixture was stirred for an additional 30 min. (R)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane (2 g, 10.6 mmol) and BF3.EtO2 (3 g, 21.1 mmol) were added and stirred at −78° C. for 4.5 hours. The reaction was then quenched by addition of aqueous ammonium chloride solution and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure to afford the desired material in a quantitative yield. The material was used in the next step with no further purification. EtO2 (3 g, 21.1 mmol) were added The reaction was then quenched by addition of aqueous ammonium chloride solution the mixture was extracted with ethyl acetate (3×50 mL) The combined organic layers were washed with brine dried (MgSO4) concentrated under reduced pressure