2-[tert-butyl(dimethyl)silyl]oxy-1-phenylethanol

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

Procedure: A mixture of (3S,4S)-3-{N-(3-phenylpropionoyl)-L-phenylalanyl}amino-4-acetoxy-azetidin-2-one (4.36 g, 10.30 mmole), 2-(tert-butyldimethylsilyl)oxy-1-phenylethanol (2.6 g, 10.30 mmole), and zinc acetate dihydrate (2.26 g, 10.30 mmole) in a mixture of benzene (70 ml) and toluene (70 ml) was refluxed overnight using Dean-Stark water separator. After cooling, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water, brine and dried over sodium sulfate. After removal of the solvent, the residue was purified by silica gel column chromatography using ethyl acetate-hexane (4:3) as eluent and (3S,4R)-3-{N-(3-phenylpropionoyl)-L-phenylalanyl}amino-4-{2-(tert-butyidimethylsilyl)oxy-1-phenyl ethoxy}-azetidin-2-one was obtained (440 mg, 7% yield). was refluxed overnight After cooling the reaction mixture was partitioned between ethyl acetate and water The organic layer was washed with water, brine dried over sodium sulfate After removal of the solvent the residue was purified by silica gel column chromatography

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

Procedure: A mixture of 1-phenyl-1,2-ethanediol (1.38 g, 10 mmole), immidazole (817 mg, 12 mmole), and tert-butylchlorodimethylsilane (1.81 g, 12 mmole) in DMF 15 (ml) was stirred at 0° C. for 1.5 hrs and then at room temperature overnight. The resulting mixture was diluted with ethyl acetate, washed with water, brine, and dried over sodium sulfate. After removal of the solvent, the residue was purified by silica gel column chromatography using ethyl acetate-hexane (1:4) as eluent. 2-(tert-butyidimethylsilyl)oxy-1-phenylethanol was obtained as an oil (2.6 g, 100% yield). at room temperature overnight washed with water, brine dried over sodium sulfate After removal of the solvent the residue was purified by silica gel column chromatography

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

Procedure: A mixture of 1-phenyl-1,2-ethanediol (1.38 g, 10 mmole), immidazole (817 mg, 12 mmole), and tert-butylchlorodimethylsilane (1.81 g, 12 mmole) in DMF 15 (ml) was stirred at 0° C. for 1.5 hrs and then at room temperature overnight. The resulting mixture was diluted with ethyl acetate, washed with water, brine, and dried over sodium sulfate. After removal of the solvent, the residue was purified by silica gel column chromatography using ethyl acetate-hexane (1:4) as eluent. 2-(tert-butyidimethylsilyl)oxy-1-phenylethanol was obtained as an oil (2.6 g, 100% yield). at room temperature overnight washed with water, brine dried over sodium sulfate After removal of the solvent the residue was purified by silica gel column chromatography

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

Procedure: Into a 250-mL 3-necked round-bottom flask was placed a solution of 1-phenylethane-1,2-diol (10 g, 72.38 mmol, 1.00 equiv), TBSCl (22 g, 145.97 mmol, 2.00 equiv) and triethylamine (14.7 g, 145.27 mmol, 2.00 equiv) in tetrahydrofuran (100 mL). The solution was stirred overnight at room temperature. The next day it was diluted with 150 mL of H2O and the mixture was extracted with 3×80 mL of ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/10). Purification afforded 17 g (93%) of 2-[(tert-butyldimethylsilyl)oxy]-1-phenylethan-1-ol as a white oil. Into a 250-mL 3-necked round-bottom flask was placed the mixture was extracted with 3×80 mL of ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum Purification

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

Procedure: Into a 250-mL 3-necked round-bottom flask was placed a solution of 1-phenylethane-1,2-diol (10 g, 72.38 mmol, 1.00 equiv), TBSCl (22 g, 145.97 mmol, 2.00 equiv) and triethylamine (14.7 g, 145.27 mmol, 2.00 equiv) in tetrahydrofuran (100 mL). The solution was stirred overnight at room temperature. The next day it was diluted with 150 mL of H2O and the mixture was extracted with 3×80 mL of ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/10). Purification afforded 17 g (93%) of 2-[(tert-butyldimethylsilyl)oxy]-1-phenylethan-1-ol as a white oil. Into a 250-mL 3-necked round-bottom flask was placed the mixture was extracted with 3×80 mL of ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum Purification

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

Procedure: To a cooled (0° C.) and stirred solution of 1-phenylethane-1,2-diol (1.0 g, 7.24 mmol) and tert-butyldimethylsilyl chloride (1.1 g, 7.24 mmol) in dichloromethane was added imidazole (0.74 g, 10.86 mmol). The reaction mixture was slowly warmed to room temperature and stirred for 20 hours. The reaction mixture was washed with water, dried, and concentrated to yield 1.8 g of 2-(tert-butyldimethylsilanyloxy)-1-phenylethanol. The reaction mixture was slowly warmed to room temperature The reaction mixture was washed with water dried concentrated

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

Procedure: To a solution of 2-(tert-butyldimethylsilanyloxy)-1-phenylethanol (0.73 g, 2.9 mmol) and 3,4-dihydro-2H pyran (486 mg, 5.78 mmol) in dichloromethane (30 ml) was added p-toluenesulfonic acid monohydrate (50 mg). The mixture was stirred at room temperature for 12 hours and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; hexane/ethyl acetate=3/1) to give tert-butyldimethyl[2-phenyl-2-(tetrahydropyran-2-yl-oxy)ethoxy]silane (0.86 g, 2.9 mmol, >99%) as a colorless oil. the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (eluent; hexane/ethyl acetate=3/1)

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

Procedure: To a solution of 2-(tert-butyldimethylsilanyloxy)-1-phenylethanone (2.5 g, 10 mmol, Example 4) in methanol (30 ml) added with sodium borohydride (378 mg, 10 mmol) at room temperature. The mixture was stirred at room temperature for 5.5 hours and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; hexane/ethyl acetate=3/1) to give 2-(tert-butyldimethylsilanyloxy)-1-phenylethanol (0.73 g, 2.9 mmol, 29%) as a colorless oil. the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (eluent; hexane/ethyl acetate=3/1)

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

Procedure: To a cooled (0° C.) and stirred solution of 1-phenylethane-1,2-diol (1.0 g, 7.24 mmol) and tert-butyldimethylsilyl chloride (1.1 g, 7.24 mmol) in dichloromethane was added imidazole (0.74 g, 10.86 mmol). The reaction mixture was slowly warmed to room temperature and stirred for 20 hours. The reaction mixture was washed with water, dried, and concentrated to yield 1.8 g of 2-(tert-butyldimethylsilanyloxy)-1-phenylethanol. The reaction mixture was slowly warmed to room temperature The reaction mixture was washed with water dried concentrated

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

Procedure: A mixture of (3S,4S)-3-{N-(3-phenylpropionoyl)-L-phenylalanyl}amino-4-acetoxy-azetidin-2-one (4.36 g, 10.30 mmole), 2-(tert-butyldimethylsilyl)oxy-1-phenylethanol (2.6 g, 10.30 mmole), and zinc acetate dihydrate (2.26 g, 10.30 mmole) in a mixture of benzene (70 ml) and toluene (70 ml) was refluxed overnight using Dean-Stark water separator. After cooling, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water, brine and dried over sodium sulfate. After removal of the solvent, the residue was purified by silica gel column chromatography using ethyl acetate-hexane (4:3) as eluent and (3S,4R)-3-{N-(3-phenylpropionoyl)-L-phenylalanyl}amino-4-{2-(tert-butyidimethylsilyl)oxy-1-phenyl ethoxy}-azetidin-2-one was obtained (440 mg, 7% yield). was refluxed overnight After cooling the reaction mixture was partitioned between ethyl acetate and water The organic layer was washed with water, brine dried over sodium sulfate After removal of the solvent the residue was purified by silica gel column chromatography

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

Procedure: A mixture of 1-phenyl-1,2-ethanediol (1.38 g, 10 mmole), immidazole (817 mg, 12 mmole), and tert-butylchlorodimethylsilane (1.81 g, 12 mmole) in DMF 15 (ml) was stirred at 0° C. for 1.5 hrs and then at room temperature overnight. The resulting mixture was diluted with ethyl acetate, washed with water, brine, and dried over sodium sulfate. After removal of the solvent, the residue was purified by silica gel column chromatography using ethyl acetate-hexane (1:4) as eluent. 2-(tert-butyidimethylsilyl)oxy-1-phenylethanol was obtained as an oil (2.6 g, 100% yield). at room temperature overnight washed with water, brine dried over sodium sulfate After removal of the solvent the residue was purified by silica gel column chromatography

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

Procedure: Into a 250-mL 3-necked round-bottom flask was placed a solution of 1-phenylethane-1,2-diol (10 g, 72.38 mmol, 1.00 equiv), TBSCl (22 g, 145.97 mmol, 2.00 equiv) and triethylamine (14.7 g, 145.27 mmol, 2.00 equiv) in tetrahydrofuran (100 mL). The solution was stirred overnight at room temperature. The next day it was diluted with 150 mL of H2O and the mixture was extracted with 3×80 mL of ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/10). Purification afforded 17 g (93%) of 2-[(tert-butyldimethylsilyl)oxy]-1-phenylethan-1-ol as a white oil. Into a 250-mL 3-necked round-bottom flask was placed the mixture was extracted with 3×80 mL of ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum Purification