tert-Butyldimethylsilyl (S)-(+)-glycidyl ether

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

Procedure: Using the (R,R)-(salen)Co(II) precatalyst of 1 (91 mg, 0.15 mmol, 0.005equiv), (+/−)-(tert-butyldimethylsilyl) glycidyl ether (5.64 g, 30.0 mmol), AcOH (32 mL, 0.6 mmol, 0.02 equiv), 0.3 mL THF, and H2O (297 mL, 16.5 mmol, 0.55 equiv) and a procedure analogous to the one outlined for 5b, (S)-(tert-butyldimethylsilyl) glycidyl ether 5c (2.72 g, 14.5 mmol, 48%) was obtained as a clear oil by vacuum distillation of the reaction mixture (30° C., 0.5 Torr). The product was determined to be present in >99% ee by derivatization through ring opening with 2-napthalenethiol in methanol using 1 equiv TEA at 0° C. and direct analysis of the 2-napthylsulfide thus obtained (Chiralcel OD, 99.25:0.75 hexanes:EtOH, 1 mL/min, 230 nm).

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

Procedure: tert-Butyl lithium (2 eq) is added to a solution of TMS-acetylene (2 eq) in THF at −78° C. and the reaction mixture stirred for an additional 30 min. (S)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane (1 eq) and BF3.EtO2 (2 eq) are added and stirred at −78° C. for 4.5 hours. The reaction is quenched by addition of aqueous ammonium chloride solution and extracted with ethyl acetate (3×). The combined organic layers are washed with brine, dried (MgSO4) and concentrated under reduced pressure to afford (S)-1-(tert-butyldimethylsilyloxy)-5-(trimethylsilyl)pent-4-yn-2-ol. EtO2 (2 eq) are added The reaction is quenched by addition of aqueous ammonium chloride solution extracted with ethyl acetate (3×) The combined organic layers are washed with brine dried (MgSO4) concentrated under reduced pressure

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

Procedure: To a solution of (R)-glycidol (5 g, 67.5 mmol) in dry dichloromethane containing triethylamine (10.3 ml, 74 mmol) cooled down to 0° C., was added a solution of tert-butyldimethylsilyl chloride (11.2 g, 74 mmol) in dry dichloromethane (30 ml). Then DMAP ( 0.33 g, 2.7 mmol) was added. The mixture was allowed to warm up to room temperature and stirred for 5 hours. The triethylammonium chloride crystals were filtered out and washed with dichloromethane (2×10 ml). The organic solution was washed with brine (2×50 ml) and dried over anhydrous sodium sulfate. The solution was concentrated and passed though a short silica gel column to remove polar impurities, and eluted with hexane/ethyl acetate (3:2). After removing the solvent, a colourless oil was collected and dried in vacuo to provide pure (S)-glycidyl-tert-butyldimethylsilyl ether (10.3 g, 81.2%). to warm up to room temperature The triethylammonium chloride crystals were filtered out washed with dichloromethane (2×10 ml) The organic solution was washed with brine (2×50 ml) dried over anhydrous sodium sulfate The solution was concentrated to remove polar impurities eluted with hexane/ethyl acetate (3:2) After removing the solvent a colourless oil was collected dried in vacuo

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

Procedure: To a solution of (R)-glycidol (5 g, 67.5 mmol) in dry dichloromethane containing triethylamine (10.3 ml, 74 mmol) cooled down to 0° C., was added a solution of tert-butyldimethylsilyl chloride (11.2 g, 74 mmol) in dry dichloromethane (30 ml). Then DMAP (0.33 g, 2.7 mmol) was added. The mixture was allowed to warm up to room temperature and stirred for 5 hours. The triethylammonium chloride crystals were filtered out and washed with dichloromethane (2×10 ml). The organic solution was washed with brine (2×50 ml) and dried over anhydrous sodium sulfate. The solution was concentrated and passed though a short silica gel column to remove polar impurities, and eluted with hexane/ethyl acetate (3:2). After removing the solvent, a colourless oil was collected and dried in vacuo to provide pure (S)-glycidyl-tert-butyldimethylsilyl ether (10.3 g, 81.2%). to warm up to room temperature The triethylammonium chloride crystals were filtered out washed with dichloromethane (2×10 ml) The organic solution was washed with brine (2×50 ml) dried over anhydrous sodium sulfate The solution was concentrated to remove polar impurities eluted with hexane/ethyl acetate (3:2) After removing the solvent a colourless oil was collected dried in vacuo

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

Procedure: To a solution of (R)-glycidol (5 g, 67.5 mmol) in dry dichloromethane containing triethylamine (10.3 ml, 74 mmol) cooled down to 0° C., was added a solution of tert-butyldimethylsilyl chloride (11.2 g, 74 mmol) in dry dichloromethane (30 ml). Then DMAP (0.33 g, 2.7 mmol) was added. The mixture was allowed to warm up to room temperature and stirred for 5 hours. The triethylammonium chloride crystals were filtered out and washed with dichloromethane (2×10 ml). The organic solution was washed with brine (2×50 ml) and dried over anhydrous sodium sulfate. The solution was concentrated and passed though a short silica gel column to remove polar impurities, and eluted with hexane/ethyl acetate (3:2). After removing the solvent, a colourless oil was collected and dried in vacuo to provide pure (S)-glycidyl-tert-butyldimethylsilyl ether (10.3 g, 81.2%). to warm up to room temperature The triethylammonium chloride crystals were filtered out washed with dichloromethane (2×10 ml) The organic solution was washed with brine (2×50 ml) dried over anhydrous sodium sulfate The solution was concentrated to remove polar impurities eluted with hexane/ethyl acetate (3:2) After removing the solvent a colourless oil was collected dried in vacuo

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

Procedure: tert-Butyl lithium (2 eq) is added to a solution of TMS-acetylene (2 eq) in THF at −78° C. and the reaction mixture stirred for an additional 30 min. (S)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane (1 eq) and BF3.EtO2 (2 eq) are added and stirred at −78° C. for 4.5 hours. The reaction is quenched by addition of aqueous ammonium chloride solution and extracted with ethyl acetate (3×). The combined organic layers are washed with brine, dried (MgSO4) and concentrated under reduced pressure to afford (S)-1-(tert-butyldimethylsilyloxy)-5-(trimethylsilyl)pent-4-yn-2-ol. EtO2 (2 eq) are added The reaction is quenched by addition of aqueous ammonium chloride solution extracted with ethyl acetate (3×) The combined organic layers are washed with brine dried (MgSO4) concentrated under reduced pressure

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: LiClO4 (7.20 g, 3 eq.) was added to a solution of tert-butyl-dimethyl-((S)-1-oxiranylmethoxy)-silane (commercial; 4.25 g, 22.6 mmol) in MeCN (70 mL). 6-amino-4H-benzo[1,4]oxazin-3-one (commercial; 3.70 g, 1 eq.) was then added and the mixture was stirred at 50° C. for 6 h. The solvent was removed under reduced pressure and the residue was purified by CC (DCM/MeOH/NH4OH 1000/25/2) to afford the title intermediate as a pale brown foam (5.25 g, 66% yield). The solvent was removed under reduced pressure the residue was purified by CC (DCM/MeOH/NH4OH 1000/25/2)

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

Procedure: Using the (R,R)-(salen)Co(II) precatalyst of 1 (91 mg, 0.15 mmol, 0.005equiv), (+/−)-(tert-butyldimethylsilyl) glycidyl ether (5.64 g, 30.0 mmol), AcOH (32 mL, 0.6 mmol, 0.02 equiv), 0.3 mL THF, and H2O (297 mL, 16.5 mmol, 0.55 equiv) and a procedure analogous to the one outlined for 5b, (S)-(tert-butyldimethylsilyl) glycidyl ether 5c (2.72 g, 14.5 mmol, 48%) was obtained as a clear oil by vacuum distillation of the reaction mixture (30° C., 0.5 Torr). The product was determined to be present in >99% ee by derivatization through ring opening with 2-napthalenethiol in methanol using 1 equiv TEA at 0° C. and direct analysis of the 2-napthylsulfide thus obtained (Chiralcel OD, 99.25:0.75 hexanes:EtOH, 1 mL/min, 230 nm).

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

Procedure: tert-Butyl lithium (2 eq) is added to a solution of TMS-acetylene (2 eq) in THF at −78° C. and the reaction mixture stirred for an additional 30 min. (S)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane (1 eq) and BF3.EtO2 (2 eq) are added and stirred at −78° C. for 4.5 hours. The reaction is quenched by addition of aqueous ammonium chloride solution and extracted with ethyl acetate (3×). The combined organic layers are washed with brine, dried (MgSO4) and concentrated under reduced pressure to afford (S)-1-(tert-butyldimethylsilyloxy)-5-(trimethylsilyl)pent-4-yn-2-ol. EtO2 (2 eq) are added The reaction is quenched by addition of aqueous ammonium chloride solution extracted with ethyl acetate (3×) The combined organic layers are washed with brine dried (MgSO4) concentrated under reduced pressure

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: LiClO4 (7.20 g, 3 eq.) was added to a solution of tert-butyl-dimethyl-((S)-1-oxiranylmethoxy)-silane (commercial; 4.25 g, 22.6 mmol) in MeCN (70 mL). 6-amino-4H-benzo[1,4]oxazin-3-one (commercial; 3.70 g, 1 eq.) was then added and the mixture was stirred at 50° C. for 6 h. The solvent was removed under reduced pressure and the residue was purified by CC (DCM/MeOH/NH4OH 1000/25/2) to afford the title intermediate as a pale brown foam (5.25 g, 66% yield). The solvent was removed under reduced pressure the residue was purified by CC (DCM/MeOH/NH4OH 1000/25/2)

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

Procedure: tert-Butyl lithium (2 eq) is added to a solution of TMS-acetylene (2 eq) in THF at −78° C. and the reaction mixture stirred for an additional 30 min. (S)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane (1 eq) and BF3.EtO2 (2 eq) are added and stirred at −78° C. for 4.5 hours. The reaction is quenched by addition of aqueous ammonium chloride solution and extracted with ethyl acetate (3×). The combined organic layers are washed with brine, dried (MgSO4) and concentrated under reduced pressure to afford (S)-1-(tert-butyldimethylsilyloxy)-5-(trimethylsilyl)pent-4-yn-2-ol. EtO2 (2 eq) are added The reaction is quenched by addition of aqueous ammonium chloride solution extracted with ethyl acetate (3×) The combined organic layers are washed with brine dried (MgSO4) concentrated under reduced pressure

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of tert-butyl-dimethyl-((S)-1-oxiranylmethoxy)-silane (commercial; 4.25 g, 22.6 mmol) in MeCN (70 mL) was added LiClO4 (7.20 g, 3 eq.). 6-amino-4H-benzo[1,4]oxazin-3-one (commercial; 3.70 g, 1 eq.) was then added and the mixture was stirred at 50° C. for 6 h. The solvent was removed under reduced pressure and the residue was purified by CC (DCM/MeOH/NH4OH 1000/25/2) to afford the title intermediate as a pale brown foam (5.25 g, 66% yield). The solvent was removed under reduced pressure the residue was purified by CC (DCM/MeOH/NH4OH 1000/25/2)