(4S)-5,5-diphenyl-4-propan-2-yl-1,3-oxazolidine-2-thione

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

Procedure: (S)-4-Isopropyl-5,5-diphenyl-oxazolidine-2-thione (412 mg, 1.39 mmol) was suspended in dichloromethane (3.3 mL), and then cooled to 0° C. in an ice bath. Dimethylaminopyridine (16 mg, 0.131 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (315 mg, 1.64 mmol) were added in this order. A solution of a commercially available reagent of (E)-10-[2-(4-phenyl-butyl)-[1,3]dioxolan-2-yl]-dec-3-enoic acid (476 mg, 1.27 mmol) in dichloromethane (3.4 mL) was then added. After stirring at 0° C. for 2 hours, an aqueous solution (50 mL) of 10% sodium dihydrogen phosphate and ethyl acetate (50 mL) were added and the mixture was separated. The organic layer was washed with a saturated aqueous solution (40 mL) of sodium chloride, then dried over anhydrous sodium sulfate, and filtered. The solvent was distilled off under reduced pressure. The residue was purified on Biotage (silica gel, n-hexane/ethyl acetate) to obtain 445 mg (0.681 mmol, 54% yield) of (E)-1-((S)-4-isopropyl-5,5-diphenyl-2-thioxo-oxazolidin-3-yl)-10-[2-(4-phenyl-butyl)-[1,3]dioxolan-2-yl]-dec-3-en-1-one (ESI (LC/MS positive mode) m/z 654 (M+H); Rt 3.07 min.). the mixture was separated The organic layer was washed with a saturated aqueous solution (40 mL) of sodium chloride dried over anhydrous sodium sulfate filtered The solvent was distilled off under reduced pressure The residue was purified on Biotage (silica gel, n-hexane/ethyl acetate)

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

Procedure: (S)-4-Isopropyl-5,5-diphenyl-oxazolidine-2-thione (2.3 g, 8.28 mmol) was suspended in dichloromethane (17.5 mL), and the mixture was then cooled to 0° C. in an ice bath. Dimethylaminopyridine (97 mg, 0.794 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.00 g, 10.4 mmol) were added and the mixture was then stirred for 25 minutes. To this suspension was added a solution of (E)-9-(2-trimethylsilanyl-ethoxycarbonylamino)-non-3-enoic acid (2.50 g, 7.92 mmol) in dichloromethane (17.5 mL). After stirring at 0° C. for 7.5 hours, an aqueous solution (50 mL) of 10% potassium dihydrogen phosphate and dichloromethane (40 mL) were added and the mixture was separated. The organic layer was washed with a saturated aqueous solution (40 mL) of sodium chloride, then dried over anhydrous sodium sulfate, and filtered. The solvent was distilled off under reduced pressure. The residue was purified on Biotage (silica gel, n-hexane/ethyl acetate) to obtain 3.01 g (5.06 mmol, yield 64%) of 2-trimethylsilanyl-ethyl [(E)-9-((S)-4-isopropyl-5,5-diphenyl-2-thioxo-oxazolidin-3-yl)-9-oxo-non-6-enyl]-carbamate. After stirring at 0° C. for 7.5 hours the mixture was separated The organic layer was washed with a saturated aqueous solution (40 mL) of sodium chloride dried over anhydrous sodium sulfate filtered The solvent was distilled off under reduced pressure The residue was purified on Biotage (silica gel, n-hexane/ethyl acetate)

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

Procedure: Under a nitrogen atmosphere, (E)-10-hexylsulfamoyl-dec-3-enoic acid (100 mg, 0.30 mmol) obtained in Step C-3 and (S)-4-isopropyl-5,5-diphenyl-oxazolidine-2-thione (89.2 mg, 0.30 mmol) were dissolved in dichloromethane (3.5 mL), and the mixture was cooled to 0° C. While maintaining the temperature at 0° C., N,N-dimethyl-4-aminopyridine (3.7 mg, 0.03 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (74.7 mg, 0.39 mmol) were added in order, and the mixture was stirred at 0° C. for 2 minutes and at room temperature for 13 hours. To the reaction solution was added an aqueous solution (4.2 mL) of 10% sodium dihydrogen phosphate and ethyl acetate and the mixture was extracted. The organic layer was washed with water and a saturated brine in order, dried over anhydrous sodium sulfate, and filtered. The solvent was distilled off. The resulting residue was then purified with SP1 (SiO2 cartridge, 20% ethyl acetate/n-hexane, Rf=0.25) to obtain the target compound, (E)-104(S)-4-isopropyl-5,5-diphenyl-2-thioxo-oxazolidin-3-yl)-10-oxo-dec-7-ene-1-sulfonic acid hexylamide (ESI (LC/MS positive mode) m/z 613 (M+H); Rt 2.60 min.; 65% purity, 96.8 mg, 53% yield). While maintaining the temperature at 0° C. the mixture was extracted The organic layer was washed with water a saturated brine in order, dried over anhydrous sodium sulfate filtered The solvent was distilled off The resulting residue was then purified with SP1 (SiO2 cartridge, 20% ethyl acetate/n-hexane, Rf=0.25)

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

Procedure: Under a nitrogen atmosphere, (E)-10-heptyloxy-dec-3-enoic acid obtained in Step C-3 (209.7 mg, 0.698 mmol) and a commercially available reagent of (S)-4-isopropyl-5,5-diphenyl-oxazolidine-2-thione (207.5 mg, 0.698 mmol) were dissolved in dichloromethane (3.13 mL), and the mixture was cooled to 0° C. While maintaining the temperature at 0° C., N,N-dimethyl-4-aminopyridine (8.5 mg, 0.0698 mmol) and WSCl (173.9 mg, 0.907 mmol) were added in order. The mixture was stirred at 0° C. for 2.0 minutes and at room temperature for 16 hours. To the reaction solution was added an aqueous solution (4.2 mL) of 10% sodium dihydrogen phosphate and the mixture was extracted with ethyl acetate. The organic layer was washed with water and a saturated brine in order, dried over anhydrous sodium sulfate, and filtered. The solvent was distilled off. The resulting residue was then purified with SP1 (SiO2 cartridge, 10% ethyl acetate/n-hexane, Rf=0.6) to obtain (E)-10-heptyloxy-1-((S)-4-isopropyl-5,5-diphenyl-2-thioxo-oxazolidin-3-yl)-dec-3-en-1-one (No. 6804254; 336.2 mg, 3 steps, 75% yield). While maintaining the temperature at 0° C. the mixture was extracted with ethyl acetate The organic layer was washed with water a saturated brine in order, dried over anhydrous sodium sulfate filtered The solvent was distilled off The resulting residue was then purified with SP1 (SiO2 cartridge, 10% ethyl acetate/n-hexane, Rf=0.6)

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

Procedure: Under a nitrogen atmosphere, (E)-11,11-difluoro-octadec-3-enoic acid (No. 6893453; 502.7 mg, 1.58 mmol) obtained in step B-4 and a commercially available reagent (S)-4-isopropyl-5,5-diphenyl-oxazolidine-2-thione (469.5 mg, 1.58 mmol) were dissolved in dichloromethane (7.5 mL), and the solution was cooled to 0° C. While maintaining the temperature at 0° C., N,N-dimethyl-4-aminopyridine (4-DMAP; 19.3 mg, 0.158 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (WSCl; 393.4 mg, 2.05 mmol) were sequentially added, and the mixture was stirred at 0° C. for 2 minutes and at room temperature for 19 hours. An aqueous solution (9.0 mL) of 10% sodium dihydrogen phosphate and ethyl acetate were added to the reaction solution before extraction. The organic layer was sequentially washed with water and a saturated brine, and dried over anhydrous sodium sulfate. After the organic layer was filtered and the solvent was distilled off, the resulting residue was purified with SP1 (SiO2 cartridge, 10% ethyl acetate/n-hexane, Rf=0.6) to obtain (E)-11,11-difluoro-1-((S)-4-isopropyl-5,5-diphenyl-2-thioxo-oxazolidin-3-yl)-octadec-3-en-1-one (No. 5547308; 647.9 mg, 3 steps, 34% yield). 502.7 mg, 1.58 mmol) obtained in step B-4 While maintaining the temperature at 0° C. The organic layer was sequentially washed with water a saturated brine, and dried over anhydrous sodium sulfate After the organic layer was filtered the solvent was distilled off the resulting residue was purified with SP1 (SiO2 cartridge, 10% ethyl acetate/n-hexane, Rf=0.6)