tert-Butyl 4-carbamothioylpiperidine-1-carboxylate → 4-[4-[5-(2,6-Difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]piperidine

A mixture of 1-tert-butoxycarbonylpiperidine-4-carbothioamide (7.33 g, 30 mmol) and 2-bromo-1-(4,5-dihydro-5-(2,6-difluorophenyl)-3-isoxazolyl)ethanone (i.e. the product of Step C) (9.12 g, 30 mmol) in acetone (100 mL) was heated at 45° C. for 3 h, and then stirred at room temperature overnight. The reaction mixture was concentrated, and the resulting residue was dissolved in dichloromethane (100 mL) and trifluoroacetic acid (40 mL), stirred at room temperature for 3 h and then concentrated under reduced pressure. The resulting oil was dissolved in aqueous hydrochloric acid solution (0.5 N, 200 mL) and extracted with ethyl acetate. The organic layer was basified by adding aqueous sodium hydroxide solution (10% in water), then washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide the title compound as a thick amber-colored oil (8.62 g, weight included residual ethyl acetate).

1. concentrationThe reaction mixture was concentrated
2. dissolutionthe resulting residue was dissolved in dichloromethane (100 mL)
3. stirringtrifluoroacetic acid (40 mL), stirred at room temperature for 3 h
4. concentrationconcentrated under reduced pressure
5. dissolutionThe resulting oil was dissolved in aqueous hydrochloric acid solution (0.5 N, 200 mL)
6. extractionextracted with ethyl acetate
7. additionby adding aqueous sodium hydroxide solution (10% in water)
8. washwashed with saturated aqueous sodium chloride solution
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure

ORD-Eintrag

ord-823fd18bce7d42428dd41ea013c778d0

Quelldatensatz

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08618137B2