Triethylamine → Ethyl 1,1-dioxo-isothiazolidine-3-carboxylate

Triethylamine (214 μL, 1.5 mmol) was added to a solution of (S)-3-(4-chloro-phenyl)-N1,N1-dimethyl-propane-1,2-diamine hydrochloride salt (Intermediate X; 182 mg, 0.73 mmol) in methanol (2 mL). The mixture was stirred for 10 min and then a solution of 2-(3-formyl-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid ethyl ester (Intermediate 8 Step 3; 190 mg, 0.61 mmol) in methanol (4 mL) was added under argon. The mixture was stirred at room temperature for 15 min and then cooled in an ice-bath. Solid sodium cyanoborohydride (57.5 mg, 0.9 mmol) and glacial acetic acid (540 μL) were added. The reaction mixture was allowed to warm to room temperature and stir. The progress of the reaction was monitored by LCMS. When the reaction was substantially complete, the solvents were evaporated and ethyl acetate (50 mL) was added. The solution was washed with washed with water (2×10 mL) and the aqueous layer was extracted with ethyl acetate (50 mL). The combined organics were dried over sodium sulfate, filtered and concentrated to give crude 2-{3-[((S)-4-chloro-phenyl)-1-dimethylaminomethyl-ethylamino)-methyl]-benzyl}-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid ethyl ester (390 mg) as a tacky yellow foam which was used directly in the next step without further purification.

1. stirringThe mixture was stirred at room temperature for 15 min
2. temperaturecooled in an ice-bath
3. stirringstir
4. customthe solvents were evaporated
5. additionethyl acetate (50 mL) was added
6. washThe solution was washed
7. washwith washed with water (2×10 mL)
8. extractionthe aqueous layer was extracted with ethyl acetate (50 mL)
9. dry with materialThe combined organics were dried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated

ORD record

ord-6ff34a015eab450385b277965d2e099c

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08314250B2