(3-phenyloxiran-2-yl)methanol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:22.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Water (800 mL), sodium hydroxide (50%, 83.1 mL), tributylmethyl-ammonium chloride (75%, 27.5 ml), and 2-ethoxyphenol (306.72 g) were combined and stirred at 20-25° C. The methylene chloride solution of 2,3-epoxy-3-phenylpropanol from Example 1 was added, and the two phase mixture was stirred and heated to 40° C. internal temperature. The methylene chloride was distilled at atmospheric pressure over a 3-4 hour period. When the methylene chloride had been removed, the internal temperature was raised to 60° C. for 2 hours. The mixture was cooled to below 30° C., toluene (1200 ml) was added, and the mixture was stirred for 5 minutes. The phases were separated and the aqueous phase was extracted with toluene (800 mL). The toluene solutions were combined and washed with 1 N NaOH (2×400 ml) and with water (400 mL) at approximately 25° C. The toluene solution was concentrated under partial vacuum maintaining an internal temperature of 40-50° C. The residual oil was dissolved in methyl t-butyl ether (760 ml), and water content was verified to be less than 0.1% by potassium fluoride assay. The solution was seeded with crystals of the title compound at 20-25° C., stirred for 1 hour, and cooled to 0° C. for 2 hours. The resulting solids were filtered, washed with methyl t-butylether (2×200 mL, cooled to −15° C.), and dried under vacuum to yield 256.1 g of the title compound (60.5% from cinnamyl alcohol). the two phase mixture was stirred heated to 40° C. internal temperature The methylene chloride was distilled at atmospheric pressure over a 3-4 hour period When the methylene chloride had been removed the internal temperature was raised to 60° C. for 2 hours The mixture was cooled to below 30° C. toluene (1200 ml) was added the mixture was stirred for 5 minutes The phases were separated the aqueous phase was extracted with toluene (800 mL) washed with 1 N NaOH (2×400 ml) and with water (400 mL) at approximately 25° C The toluene solution was concentrated under partial vacuum maintaining an internal temperature of 40-50° C The residual oil was dissolved in methyl t-butyl ether (760 ml) was seeded with crystals of the title compound at 20-25° C. stirred for 1 hour cooled to 0° C. for 2 hours The resulting solids were filtered washed with methyl t-butylether (2×200 mL, cooled to −15° C.) dried under vacuum

Conditions: temp:17.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium carbonate (224 g) and trans-cinnamyl alcohol (200.0 g) were mixed with 2 L of methylene chloride, a slow nitrogen sweep was maintained through the vapor space of the flask and the mixture was cooled to 15-20° C. with a cold water bath. Peracetic acid solution (35%, 381.2 mL) was added over a 3 hour period, maintaining the internal temperature below 25° C. After the peracetic acid addition was complete, the mixture was stirred for 2-3 hours until complete, as shown by HPLC analysis. The mixture was cooled to 10° C. with an ice bath, and a solution of sodium sulfite (160 g) in 1200 ml water was added slowly over 90 minutes, keeping the temperature below 30° C. The phases were separated and the aqueous phase was extracted with methylene chloride (200 mL) to give a solution of the title compound. a slow nitrogen sweep was maintained through the vapor space of the flask maintaining the internal temperature below 25° C The mixture was cooled to 10° C. with an ice bath the temperature below 30° C The phases were separated the aqueous phase was extracted with methylene chloride (200 mL)

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A solution of 1.00 g (6.62 mmol) of 4-methoxyindoline (Gangjee et al., J. Med. Chem. 1997, 40, 479-485) and 1.90 g (8.51 mmol) of magnesium perchlorate in 20 mL of CH3CN was treated in a dropwise manner with a solution of 1.00 g (6.62 mmol) of 2,3-epoxy-3-phenyl-1-propanol (Ogata and Tomizawa, Bull. Chim. Soc. Jap. 1977, 50, 261-265) in 10 mL of CH3CN. The reaction was stirred at ambient temperature for 2.5 hours and was diluted with 30 mL of saturated aqueous NaHCO3. The organic layer was separated and the aqueous phase was extracted with EtOAc (2×20 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The oil was purified by radial chromatography (SiO2; 10% then 20% then 30% EtOAc in hexanes) to afford 1.55 g (5.17 mmol; 78%) of the subtitled compound as a solid. The organic layer was separated the aqueous phase was extracted with EtOAc (2×20 mL) The combined organic layers were dried (Na2SO4) filtered concentrated in vacuo The oil was purified by radial chromatography (SiO2

Conditions: temp:22.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Water (800 mL), sodium hydroxide (50%, 83.1 mL), tributylmethyl-ammonium chloride (75%, 27.5 ml), and 2-ethoxyphenol (306.72 g) were combined and stirred at 20-25° C. The methylene chloride solution of 2,3-epoxy-3-phenylpropanol from Example 1 was added, and the two phase mixture was stirred and heated to 40° C. internal temperature. The methylene chloride was distilled at atmospheric pressure over a 3-4 hour period. When the methylene chloride had been removed, the internal temperature was raised to 60° C. for 2 hours. The mixture was cooled to below 30° C., toluene (1200 ml) was added, and the mixture was stirred for 5 minutes. The phases were separated and the aqueous phase was extracted with toluene (800 mL). The toluene solutions were combined and washed with 1 N NaOH (2×400 ml) and with water (400 mL) at approximately 25° C. The toluene solution was concentrated under partial vacuum maintaining an internal temperature of 40-50° C. The residual oil was dissolved in methyl t-butyl ether (760 ml), and water content was verified to be less than 0.1% by potassium fluoride assay. The solution was seeded with crystals of the title compound at 20-25° C., stirred for 1 hour, and cooled to 0° C. for 2 hours. The resulting solids were filtered, washed with methyl t-butylether (2×200 mL, cooled to −15° C.), and dried under vacuum to yield 256.1 g of the title compound (60.5% from cinnamyl alcohol). the two phase mixture was stirred heated to 40° C. internal temperature The methylene chloride was distilled at atmospheric pressure over a 3-4 hour period When the methylene chloride had been removed the internal temperature was raised to 60° C. for 2 hours The mixture was cooled to below 30° C. toluene (1200 ml) was added the mixture was stirred for 5 minutes The phases were separated the aqueous phase was extracted with toluene (800 mL) washed with 1 N NaOH (2×400 ml) and with water (400 mL) at approximately 25° C The toluene solution was concentrated under partial vacuum maintaining an internal temperature of 40-50° C The residual oil was dissolved in methyl t-butyl ether (760 ml) was seeded with crystals of the title compound at 20-25° C. stirred for 1 hour cooled to 0° C. for 2 hours The resulting solids were filtered washed with methyl t-butylether (2×200 mL, cooled to −15° C.) dried under vacuum

Conditions: temp:17.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium carbonate (224 g) and trans-cinnamyl alcohol (200.0 g) were mixed with 2 L of methylene chloride, a slow nitrogen sweep was maintained through the vapor space of the flask and the mixture was cooled to 15-20° C. with a cold water bath. Peracetic acid solution (35%, 381.2 mL) was added over a 3 hour period, maintaining the internal temperature below 25° C. After the peracetic acid addition was complete, the mixture was stirred for 2-3 hours until complete, as shown by HPLC analysis. The mixture was cooled to 10° C. with an ice bath, and a solution of sodium sulfite (160 g) in 1200 ml water was added slowly over 90 minutes, keeping the temperature below 30° C. The phases were separated and the aqueous phase was extracted with methylene chloride (200 mL) to give a solution of the title compound. a slow nitrogen sweep was maintained through the vapor space of the flask maintaining the internal temperature below 25° C The mixture was cooled to 10° C. with an ice bath the temperature below 30° C The phases were separated the aqueous phase was extracted with methylene chloride (200 mL)