(2S)-propane-1,2-diol

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Triethylamine was added to methylene chloride solution of (2S)-propane-1,2-diol, and then methylene chloride solution of p-toluenesulfonyl chloride was added thereto at −20° C. and stirred at room temperature for 18 hours to obtain (2S)-2-hydroxypropyl-4-methylbenzene sulfonate.

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

Procedure: (S)-propane-1,2-diol (52 mg, 0.68 mmol) in THF (1 mL) was treated with NaH (60% dispersion; 27 mg, 0.68 mmol) at room temperature for 20 minutes. The mixture was cooled to 0° C. and a solution of Example 20B (90 mg, 0.23 mmol) in THF (1 mL) was added. The mixture was allowed to warm to room temperature, and stirred for 4 hours. The mixture was diluted with saturated aqueous NaHCO3 (20 mL) and extracted with ethyl acetate (2×30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-100% ethyl acetate in hexanes) to afford 19 mg (19%) of the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 1.04 (t, J=7.48 Hz, 3H) 1.28 (d, J=6.41 Hz, 3H) 1.47-1.59 (m, 2H) 1.88-1.98 (m, 2H) 3.87 (t, J=8.85 Hz, 1H) 4.21-4.31 (m, 1H) 4.35 (dd, J=9.15, 2.75 Hz, 1H) 4.51-4.59 (m, 2H) 7.12 (d, J=8.85 Hz, 1H) 7.72 (dd, J=8.54, 2.14 Hz, 2H) 8.51 (d, J=1.83 Hz, 2H) 8.75 (s, 1H); MS (DCI/NH3) m/z 454 (M+H)+. to warm to room temperature extracted with ethyl acetate (2×30 mL) The combined organic extracts were dried over anhydrous Na2SO4 filtered concentrated The residue was purified by column chromatography

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:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (s)-(+)-1,2-propanediol (2.0 g, 26.3 mmol) in DMF (5 mL) was added TBS-Cl (5.94 g, 39.4 mmol) and imidazole (2.147 g, 31.5 mmol). The reaction was stirred at 25° C. for 18 h. The reaction mixture was partitioned between ethyl acetate and sat. ammonium chloride. The organic phase was washed with sat ammonium chloride and brine, dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash chromatography to give 33A (4.0 g, 80% yield) as a colorless oil. The reaction mixture was partitioned between ethyl acetate and sat. ammonium chloride The organic phase was washed with sat ammonium chloride and brine dried (MgSO4) concentrated in vacuo The crude product was purified by flash chromatography

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Triethylamine was added to methylene chloride solution of (2S)-propane-1,2-diol, and then methylene chloride solution of p-toluenesulfonyl chloride was added thereto at −20° C. and stirred at room temperature for 18 hours to obtain (2S)-2-hydroxypropyl-4-methylbenzene sulfonate.

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

Procedure: (S)-propane-1,2-diol (52 mg, 0.68 mmol) in THF (1 mL) was treated with NaH (60% dispersion; 27 mg, 0.68 mmol) at room temperature for 20 minutes. The mixture was cooled to 0° C. and a solution of Example 20B (90 mg, 0.23 mmol) in THF (1 mL) was added. The mixture was allowed to warm to room temperature, and stirred for 4 hours. The mixture was diluted with saturated aqueous NaHCO3 (20 mL) and extracted with ethyl acetate (2×30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-100% ethyl acetate in hexanes) to afford 19 mg (19%) of the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 1.04 (t, J=7.48 Hz, 3H) 1.28 (d, J=6.41 Hz, 3H) 1.47-1.59 (m, 2H) 1.88-1.98 (m, 2H) 3.87 (t, J=8.85 Hz, 1H) 4.21-4.31 (m, 1H) 4.35 (dd, J=9.15, 2.75 Hz, 1H) 4.51-4.59 (m, 2H) 7.12 (d, J=8.85 Hz, 1H) 7.72 (dd, J=8.54, 2.14 Hz, 2H) 8.51 (d, J=1.83 Hz, 2H) 8.75 (s, 1H); MS (DCI/NH3) m/z 454 (M+H)+. to warm to room temperature extracted with ethyl acetate (2×30 mL) The combined organic extracts were dried over anhydrous Na2SO4 filtered concentrated The residue was purified by column chromatography

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

Procedure: (S)-propane-1,2-diol (52 mg, 0.68 mmol) in THF (1 mL) was treated with NaH (60% dispersion; 27 mg, 0.68 mmol) at room temperature for 20 minutes. The mixture was cooled to 0° C. and a solution of Example 18B (90 mg, 0.23 mmol) in THF (1 mL) was added. The mixture was allowed to warm to room temperature, and stirred for 4 hours. The mixture was diluted with saturated aqueous NaHCO3 (20 mL) and extracted with ethyl acetate (2×30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-100% ethyl acetate in hexanes) to afford 19 mg (19%) of the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 1.04 (t, J=7.48 Hz, 3H) 1.28 (d, J=6.41 Hz, 3H) 1.47-1.59 (m, 2H) 1.88-1.98 (m, 2H) 3.87 (t, J=8.85 Hz, 1H) 4.21-4.31 (m, 1H) 4.35 (dd, J=9.15, 2.75 Hz, 1H) 4.51-4.59 (m, 2H) 7.12 (d, J=8.85 Hz, 1H) 7.72 (dd, J=8.54, 2.14 Hz, 2H) 8.51 (d, J=1.83 Hz, 2H) 8.75 (s, 1H); MS (DCI/NH3) m/z 454 (M+H)+. to warm to room temperature extracted with ethyl acetate (2×30 mL) The combined organic extracts were dried over anhydrous Na2SO4 filtered concentrated The residue was purified by column chromatography

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

Procedure: A solution of 3,4-dimethoxythiophene (5.18 g), (S)-1,2-propanediol (3.0 g) and p-toluenesulfonic acid monohydrate (100 mg) in toluene (50 ml) was heated at 95° C. during which a continuous stream of nitrogen was passed over the solution. After 30 h the reaction mixture was poured into ethyl acetate, washed with NaHCO3 and the organic phase was concentrated. Subsequent filtration over SiO2 using n-hexane as eluant resulted in pure product (3.90 g). GC-MS: 156 (purity>99%); 1H-NMR (CDCl3): δ 6.30 (2×d, 2H), 4.26 (m, 1H), 4.15 (dd, 1H), 3.82 (dd, 1H), 1.35 (d, 3H) ppm; specific rotation [α]=−46° at 25° C. and 436 nm in hexane (c=0.066). washed with NaHCO3 the organic phase was concentrated Subsequent filtration over SiO2

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

Procedure: (S)-propane-1,2-diol (52 mg, 0.68 mmol) in THF (1 mL) was treated with NaH (60% dispersion; 27 mg, 0.68 mmol) at room temperature for 20 minutes. The mixture was cooled to 0° C. and a solution of Example 18B (90 mg, 0.23 mmol) in THF (1 mL) was added. The mixture was allowed to warm to room temperature, and stirred for 4 hours. The mixture was diluted with saturated aqueous NaHCO3 (20 mL) and extracted with ethyl acetate (2×30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-100% ethyl acetate in hexanes) to afford 19 mg (19%) of the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 1.04 (t, J=7.48 Hz, 3H) 1.28 (d, J=6.41 Hz, 3H) 1.47-1.59 (m, 2H) 1.88-1.98 (m, 2H) 3.87 (t, J=8.85 Hz, 1H) 4.21-4.31 (m, 1H) 4.35 (dd, J=9.15, 2.75 Hz, 1H) 4.51-4.59 (m, 2H) 7.12 (d, J=8.85 Hz, 1H) 7.72 (dd, J=8.54, 2.14 Hz, 2H) 8.51 (d, J=1.83 Hz, 2H) 8.75 (s, 1H); MS (DCI/NH3) m/z 454 (M+H)+. to warm to room temperature extracted with ethyl acetate (2×30 mL) The combined organic extracts were dried over anhydrous Na2SO4 filtered concentrated The residue was purified by column chromatography

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

Procedure: A solution of 3,4-dimethoxythiophene (5.18 g), (S)-1,2-propanediol (3.0 g) and p-toluenesulfonic acid monohydrate (100 mg) in toluene (50 ml) was heated at 95° C. during which a continuous stream of nitrogen was passed over the solution. After 30 h the reaction mixture was poured into ethyl acetate, washed with NaHCO3 and the organic phase was concentrated. Subsequent filtration over SiO2 using n-hexane as eluant resulted in pure product (3.90 g). GC-MS: 156 (purity>99%); 1H-NMR (CDCl3): δ 6.30 (2×d, 2H), 4.26 (m, 1H), 4.15 (dd, 1H), 3.82 (dd, 1H), 1.35 (d, 3H) ppm; specific rotation [α]=−46° at 25° C. and 436 nm in hexane (c=0.066). washed with NaHCO3 the organic phase was concentrated Subsequent filtration over SiO2