(2S)-1-[tert-butyl(dimethyl)silyl]oxypropan-2-ol

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

Procedure: To a solution of 2-methylquinolin-8-ol (0.40 g, 2.5 mmol) in tetrahydrofuran (2.1 mL, 2.5 mmol) was added triphenylphosphine (1.6 g, 6.3 mmol), diethyl azodicarboxylate (0.63 mL, 4.0 mmol), and (S)-1-(tert-butyldimethylsilyloxy)propan-2-ol (0.62 g, 3.3 mmol). The resultant mixture was allowed to stir at ambient temperature for 24 hours. The reaction mixture was diluted with water (10 mL) and extracted with dichloromethane (2×20 mL). The combined organic extracts were dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by normal phase chromatography on silica gel (10-30% ethyl acetate/hexanes) to provide the title compound (0.33 g, 40%). extracted with dichloromethane (2×20 mL) The combined organic extracts were dried over magnesium sulfate concentrated under reduced pressure The residue was purified by normal phase chromatography on silica gel (10-30% ethyl acetate/hexanes)

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

Procedure: A solution of (S)-propane-1,2-diol (1.9 mL, 26 mmol), tert-butyldimethylsilyl chloride (4.87 g, 32 mmol), and imidazole (4.5 g, 66 mmol) in anhydrous dimethylformamide (6.6 mL, 26 mmol) was allowed to stir at ambient temperature for 12 hours. The reaction mixture was poured into ethyl acetate (50 mL) and washed sequentially with saturated aqueous sodium bicarbonate (30 mL) and water (30 mL). The organic extract was dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound (5.2 g, 104%) which was used without further purification. washed sequentially with saturated aqueous sodium bicarbonate (30 mL) and water (30 mL) The organic extract was dried over sodium sulfate filtered concentrated under reduced pressure

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium trifluoromethanesulfonate (0.974 g, 3.02 mmol) was added in one portion to (S)-methyl oxirane-2-carboxylate (1.234 g, 12.08 mmol) and (S)-1-(tert-butyldimethylsilyloxy)propan-2-ol (CAS no. 113534-13-7) (2.30 g, 12.08 mmol) in EtOAc (5 mL) cooled to 10° C. The resulting suspension was stirred at 10° C. for 10 minutes and then warmed to 45° C. and stirred for 2 days. The crude product was purified by flash silica chromatography, eluting with 0 to 30% EtOAc in isohexane to afford the product (1.336 g, 37.8%). 1H NMR (400 MHz, DMSO) δ0.00 (s, 6H), 0.83 (s, 9H), 0.98 (d, 3H), 3.34-3.53 (m, 3H), 3.55-3.64 (m, 5H), 4.11 (q, 1H), 5.39 (d, 1H) warmed to 45° C. stirred for 2 days The crude product was purified by flash silica chromatography eluting with 0 to 30% EtOAc in isohexane

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

Procedure: A similar procedure as detailed above for Compound 133 was used. 1-(2-fluoro-5-nitrophenyl)-4-methyl-1,4-dihydro-5H-tetrazol-5-one (prepared according to US patent application 20110130415) (239 mg, 1.0 mmol), potassium tert-butoxide (146 mg, 1.2 mmol) and (S)-1-((tert-butyldimethylsilyl)oxy)propan-2-ol (Milestone PharmaTech) (209 mg, 1.1 mmol) in THF (10 mL) was stirred for 2 hr at room temperature to give the product after workup (yield assumed quantitative=410 mg). The product was used in the next step without further purification. to give the product after workup (yield assumed quantitative=410 mg) The product was used in the next step without further purification

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

Procedure: A similar procedure as detailed above for Compound 133 was used. 1-(2-fluoro-5-nitrophenyl)-4-methyl-1,4-dihydro-5H-tetrazol-5-one (prepared according to US patent application 20110130415) (239 mg, 1.0 mmol), potassium tert-butoxide (146 mg, 1.2 mmol) and (S)-1-((tert-butyldimethylsilyl)oxy)propan-2-ol (Milestone PharmaTech) (209 mg, 1.1 mmol) in THF (10 mL) was stirred for 2 hr at room temperature to give the product after workup (yield assumed quantitative=410 mg). The product was used in the next step without further purification. to give the product after workup (yield assumed quantitative=410 mg) The product was used in the next step without further purification

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

Procedure: To a solution of 2-methylquinolin-8-ol (0.40 g, 2.5 mmol) in tetrahydrofuran (2.1 mL, 2.5 mmol) was added triphenylphosphine (1.6 g, 6.3 mmol), diethyl azodicarboxylate (0.63 mL, 4.0 mmol), and (S)-1-(tert-butyldimethylsilyloxy)propan-2-ol (0.62 g, 3.3 mmol). The resultant mixture was allowed to stir at ambient temperature for 24 hours. The reaction mixture was diluted with water (10 mL) and extracted with dichloromethane (2×20 mL). The combined organic extracts were dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by normal phase chromatography on silica gel (10-30% ethyl acetate/hexanes) to provide the title compound (0.33 g, 40%). extracted with dichloromethane (2×20 mL) The combined organic extracts were dried over magnesium sulfate concentrated under reduced pressure The residue was purified by normal phase chromatography on silica gel (10-30% ethyl acetate/hexanes)

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

Procedure: A solution of (S)-propane-1,2-diol (1.9 mL, 26 mmol), tert-butyldimethylsilyl chloride (4.87 g, 32 mmol), and imidazole (4.5 g, 66 mmol) in anhydrous dimethylformamide (6.6 mL, 26 mmol) was allowed to stir at ambient temperature for 12 hours. The reaction mixture was poured into ethyl acetate (50 mL) and washed sequentially with saturated aqueous sodium bicarbonate (30 mL) and water (30 mL). The organic extract was dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound (5.2 g, 104%) which was used without further purification. washed sequentially with saturated aqueous sodium bicarbonate (30 mL) and water (30 mL) The organic extract was dried over sodium sulfate filtered concentrated under reduced pressure

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

Procedure: A solution of (S)-propane-1,2-diol (1.9 mL, 26 mmol), tert-butyldimethylsilyl chloride (4.87 g, 32 mmol), and imidazole (4.5 g, 66 mmol) in anhydrous dimethylformamide (6.6 mL, 26 mmol) was allowed to stir at ambient temperature for 12 hours. The reaction mixture was poured into ethyl acetate (50 mL) and washed sequentially with saturated aqueous sodium bicarbonate (30 mL) and water (30 mL). The organic extract was dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound (5.2 g, 104%) which was used without further purification. washed sequentially with saturated aqueous sodium bicarbonate (30 mL) and water (30 mL) The organic extract was dried over sodium sulfate filtered concentrated under reduced pressure

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

Procedure: A similar procedure as detailed above for Compound 133 was used. 1-(2-fluoro-5-nitrophenyl)-4-methyl-1,4-dihydro-5H-tetrazol-5-one (prepared according to US patent application 20110130415) (239 mg, 1.0 mmol), potassium tert-butoxide (146 mg, 1.2 mmol) and (S)-1-((tert-butyldimethylsilyl)oxy)propan-2-ol (Milestone PharmaTech) (209 mg, 1.1 mmol) in THF (10 mL) was stirred for 2 hr at room temperature to give the product after workup (yield assumed quantitative=410 mg). The product was used in the next step without further purification. to give the product after workup (yield assumed quantitative=410 mg) The product was used in the next step without further purification

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

Procedure: To a mixture of 4,5-dihydro-2-(3-hydroxyphenyl)-4(R)-phenyloxazole (5.0 g, 20.9 mmol), 1-(tert-butyldimethylsilyloxy)propan-2(S)-ol (4.76 g, 25 mmol) and triphenylphosphine (6.58 g, 25 mmol) in dry tetrahydrofuran (30 ml) was added dropwise a solution of diethyl azodicarboxylate (3.9 ml, 25 mmol) in dry tetra-hydrofuran (5 ml). The reaction mixture was stirred ambient temperature for 1 h and then ay 50° C. for 5 hours. Volatiles were removed by evaporation and the resulting residue purified by column chromatography on silica gel eluting with ethyl acetate-hexane (=1:6) to afford 1-(tert-butyldimethylsilyloxy)-2(R)-[3-(4,5-dihydro-4(R)-phenyloxazol-2-yl)phenoxy]propane (8.7 g, quant.) as a colorless oil. ay 50° C. for 5 hours Volatiles were removed by evaporation the resulting residue purified by column chromatography on silica gel eluting with ethyl acetate-hexane (=1:6)

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium trifluoromethanesulfonate (0.974 g, 3.02 mmol) was added in one portion to (S)-methyl oxirane-2-carboxylate (1.234 g, 12.08 mmol) and (S)-1-(tert-butyldimethylsilyloxy)propan-2-ol (CAS no. 113534-13-7) (2.30 g, 12.08 mmol) in EtOAc (5 mL) cooled to 10° C. The resulting suspension was stirred at 10° C. for 10 minutes and then warmed to 45° C. and stirred for 2 days. The crude product was purified by flash silica chromatography, eluting with 0 to 30% EtOAc in isohexane to afford the product (1.336 g, 37.8%). 1H NMR (400 MHz, DMSO) δ0.00 (s, 6H), 0.83 (s, 9H), 0.98 (d, 3H), 3.34-3.53 (m, 3H), 3.55-3.64 (m, 5H), 4.11 (q, 1H), 5.39 (d, 1H) warmed to 45° C. stirred for 2 days The crude product was purified by flash silica chromatography eluting with 0 to 30% EtOAc in isohexane

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

Procedure: To a solution of 2-methylquinolin-8-ol (0.40 g, 2.5 mmol) in tetrahydrofuran (2.1 mL, 2.5 mmol) was added triphenylphosphine (1.6 g, 6.3 mmol), diethyl azodicarboxylate (0.63 mL, 4.0 mmol), and (S)-1-(tert-butyldimethylsilyloxy)propan-2-ol (0.62 g, 3.3 mmol). The resultant mixture was allowed to stir at ambient temperature for 24 hours. The reaction mixture was diluted with water (10 mL) and extracted with dichloromethane (2×20 mL). The combined organic extracts were dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by normal phase chromatography on silica gel (10-30% ethyl acetate/hexanes) to provide the title compound (0.33 g, 40%). extracted with dichloromethane (2×20 mL) The combined organic extracts were dried over magnesium sulfate concentrated under reduced pressure The residue was purified by normal phase chromatography on silica gel (10-30% ethyl acetate/hexanes)