Trifluoroacetic acid → 4-[2-Methoxyethylthio]-3,3-diethyl-2-azetidinone

To S-triphenylmethyl 2-methoxyethanethiol (1.37 g, 4.1 mmol) in dichloromethane (30 ml) under nitrogen were added triethylsilane (0.953 g, 1.31 ml, 8.2 mmol) and trifluoroacetic acid (0.632 ml, 0.935 g, 8.2 mmol). The mixture was stirred at room temperature for 16 hours. Acetone (50 ml) was added and the mixture neutralised with 2 M aqueous sodium hydroxide. 1 M Aqueous sodium hydroxide (24 ml, 24 mmol), 4-acetoxy-3,3-diethyl-2-azetidinone (J. Med. Chem., 35, 3745-3754 (1992)) (0.690 g, 6.00 mmol) and acetone (10 ml) were then added and the mixture stirred at room temperature for 23 hours. The solvents were removed in vacuo and to the residue were added water (50 ml) and dichloromethane (50 ml). The organic layer was isolated and the water layer extracted further with dichloromethane (3×30 ml). The 4 organic layers were combined and washed with water (30 ml) and saturated brine (30 ml), dried (Na2SO4) and concentrated in vacuo. Purification by flash column chromatography (gradient from petrol/EtOAc, 9:1 to EtOAc) gave the title compound (0.51 g, 63%) as an oil.

1. stirringthe mixture stirred at room temperature for 23 hours
2. customThe solvents were removed in vacuo and to the residue
3. additionwere added water (50 ml) and dichloromethane (50 ml)
4. customThe organic layer was isolated
5. extractionthe water layer extracted further with dichloromethane (3×30 ml)
6. washwashed with water (30 ml) and saturated brine (30 ml)
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated in vacuo
9. customPurification by flash column chromatography (gradient from petrol/EtOAc, 9:1 to EtOAc)

ORD record

ord-e213af0f64364fb2906065bad0713464

Source dataset

uspto-grants-2002_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06375926B1