(4R)-4-methyloxetan-2-one

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

Procedure: To a magnetically-stirred 25 mL round-bottomed flask blanketed with nitrogen was charged 2-mercaptothiophene (0.73 g, 6.29 mmol) in tetrahydrofuran (7 mL, K.F. <0.1 mg/mL) at 25° C. Triethylamine (0.87 mL, 6.29 mmol) was injected and the reaction mixture was stirred for 10 minutes to complete salt formation. To this mixture was added (R)-(+)-β-methyl-β-propiolactone (0.54 g, 6.29 mmol) in one portion and the reaction mixture was stirred at 25° C. for approximately 3 hours. When complete, the mixture was stripped of solvent on a rotary evaporator at 25° C. and diluted with ethyl acetate (10 mL) and water (10 mL). The pH of the mixture was then adjusted to 2.0 with 5N hydrochloric acid and the layers separated. The upper ethyl acetate product layer was dried over sodium sulfate and concentrated to an oil on a rotary evaporator. Silica gel chromatography (10% ethyl acetate/hexanes) afforded 1.19 g of (S)-3-(2-thienylthio)butyric acid (94%). To a magnetically-stirred 25 mL round-bottomed flask blanketed with nitrogen the reaction mixture was stirred at 25° C. for approximately 3 hours When complete, the mixture was stripped of solvent on a rotary evaporator at 25° C. diluted with ethyl acetate (10 mL) and water (10 mL) the layers separated The upper ethyl acetate product layer was dried over sodium sulfate concentrated to an oil on a rotary evaporator

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

Procedure: To a magnetically-stirred 25 mL round-bottomed flask blanketed with nitrogen was charged 2-mercaptothiophene (0.73 g, 6.29 mmol) in tetrahydrofuran (7 mL, K.F. <0.1 mg/mL) at 25° C. Triethylamine (0.87 mL, 6.29 mmol) was injected and the reaction mixture was stirred for 10 minutes to complete salt formation. To this mixture was added (R)-(+)-β-methyl-β-propiolactone (0.54 g, 6.29 mmol) in one portion and the reaction mixture was stirred at 25° C. for approximately 3 hours. When complete, the mixture was stripped of solvent on a rotary evaporator at 25° C. and diluted with ethyl acetate (10 mL) and water (10 mL). The pH of the mixture was then adjusted to 2.0 with 5N hydrochloric acid and the layers separated. The upper ethyl acetate product layer was dried over sodium sulfate and concentrated to an oil on a rotary evaporator. Silica gel chromatography (10% ethyl acetate/hexanes) afforded 1.19 g of (S)-3-(2-thienylthio)butyric acid (94%). To a magnetically-stirred 25 mL round-bottomed flask blanketed with nitrogen the reaction mixture was stirred at 25° C. for approximately 3 hours When complete, the mixture was stripped of solvent on a rotary evaporator at 25° C. diluted with ethyl acetate (10 mL) and water (10 mL) the layers separated The upper ethyl acetate product layer was dried over sodium sulfate concentrated to an oil on a rotary evaporator

Conditions: temp:80.84999847412111; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A jacketed 30-L 3-neck bottom-valve cylindrical reactor equipped with overhead stirrer, reflux condenser, addition funnel, and N2 inlet was flushed with N2. Water (8.7 L) was charged followed by aniline (423 L, 4.9 mol). Stirring was initiated and the internal temperature set for 80° C. After the internal temperature reached 77° C., (R)-β-butyrolactone was charged over 1.5 h via addition funnel. The internal temperature was maintained between 80-81.7° C. during the course of addition. Once addition was completed, reaction was cooled to 20° C. over 1 h. K2CO3 (250 g, 1.8 mol, 0.75 equiv) was charged as a solid, and the aqueous pH was determined to be 10. The aqueous phase was extracted with MTBE (3×2 L), and the extracts were discarded. After adjusting the pH of the aqueous phase to 5 with 6 N HCl (225 mL), it was extracted with EtOAc (3×2 L). After each extraction, the pH was checked and was readjusted to 5 with 6 N HCl as necessary. The combined EtOAc extracts were washed with saturated brine (2 L), dried with MgSO4, and concentrated via rotary evaporation to produce a pink oil. Recovery: 300 g (72%). Enantiomeric excess was determined by chiral HPLC to be 94%. A jacketed 30-L 3-neck bottom-valve cylindrical reactor equipped with overhead stirrer reflux condenser, addition funnel, and N2 inlet was flushed with N2 Water (8.7 L) was charged set for 80° C reached 77° C. Once addition reaction was cooled to 20° C. over 1 h The aqueous phase was extracted with MTBE (3×2 L) was extracted with EtOAc (3×2 L) After each extraction The combined EtOAc extracts were washed with saturated brine (2 L) dried with MgSO4 concentrated via rotary evaporation to produce a pink oil

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

Procedure: To a magnetically-stirred 25 mL round-bottomed flask blanketed with nitrogen was charged 2-mercaptothiophene (0.73 g, 6.29 mmol) in tetrahydrofuran (7 mL, K.F. <0.1 mg/mL) at 25° C. Triethylamine (0.87 mL, 6.29 mmol) was injected and the reaction mixture was stirred for 10 minutes to complete salt formation. To this mixture was added (R)-(+)-β-methyl-β-propiolactone (0.54 g, 6.29 mmol) in one portion and the reaction mixture was stirred at 25° C. for approximately 3 hours. When complete, the mixture was stripped of solvent on a rotary evaporator at 25° C. and diluted with ethyl acetate (10 mL) and water (10 mL). The pH of the mixture was then adjusted to 2.0 with 5N hydrochloric acid and the layers separated. The upper ethyl acetate product layer was dried over sodium sulfate and concentrated to an oil on a rotary evaporator. Silica gel chromatography (10% ethyl acetate/hexanes) afforded 1.19 g of (S)-3-(2-thienylthio)butyric acid (94%). To a magnetically-stirred 25 mL round-bottomed flask blanketed with nitrogen the reaction mixture was stirred at 25° C. for approximately 3 hours When complete, the mixture was stripped of solvent on a rotary evaporator at 25° C. diluted with ethyl acetate (10 mL) and water (10 mL) the layers separated The upper ethyl acetate product layer was dried over sodium sulfate concentrated to an oil on a rotary evaporator