Triethylamine → Tert-butyl 3-(1-{[3-(trifluoromethyl)phenyl]thio}ethyl)azetidine-1-carboxylate

To 100 ml round bottom flask was added tert-butyl 3-(1-hydroxyethyl)azetidine-1-carboxylate (2.06 g, 10.2 mmol), triethylamine (4.2 ml, 30.7 mmol) and 40 ml dichloromethane. Methanesulfonyl chloride (0.955 ml, 12.3 mmol) was added at 0° C. The reaction mixture was allowed to warm up to room temperature and stirred for 1 hour. It was then diluted with 100 ml ether, washed with 2×50 ml saturated sodium carbonate solution. The organics were dried over sodium sulfate, filtered and concentrated. The residue was dissolved in 30 ml dimethylformamide. Potassium carbonate (3.75 g, 26.8 mmol) and 3-(trifluoromethyl)benzenethiol (1.91 g, 10.7 mmol) were added. The resulting reaction mixture was heated at 75° C. overnight. It was diluted with 120 ml ether, washed sequentially with 150 ml water, and 75 ml saturated sodium carbonate. The organics were dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel column eluted with hexane to 1:9 ethyl acetate/hexane to give 2.65 g desired product as colorless oil.

1. washwashed with 2×50 ml saturated sodium carbonate solution
2. dry with materialThe organics were dried over sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated
5. dissolutionThe residue was dissolved in 30 ml dimethylformamide
6. customThe resulting reaction mixture
7. temperaturewas heated at 75° C. overnight
8. washwashed sequentially with 150 ml water, and 75 ml saturated sodium carbonate
9. dry with materialThe organics were dried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was purified on silica gel column
13. washeluted with hexane to 1:9 ethyl acetate/hexane

ORD record

ord-701bb164e4f6493fa99ec790b112630a

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08304434B2