Triethylamine → (S)-tert-butyl 3-(acetylthiomethyl)-4-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)piperazine-1-carboxylate

To the solution of (S)-tert-butyl 4-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-(hydroxymethyl)piperazine-1-carboxylate (817 mg, 2.01 mmol) in anhydrous THF (20 mL) under nitrogen atmosphere at 0° C. was added anhydrous triethylamine (0.560 mL, 4.02 mmol), followed by addition of methanesulfonyl chloride (0.234 mL, 3.01 mmol) and 4-dimethylaminopyridine (24.6 mg, 0.201 mmol). The ice bath removed and reaction mixture was stirred for 2 hours. Resulting mixture was then concentrated under reduced pressure. Resulting oil was redissolved in anhydrous DMSO (13 mL) and treated with potassium thioacetate (1235 mg, 10.81 mmol). The reaction mixture was stirred at room temperature under nitrogen for 2 hours. The mixture was diluted with ethyl acetate, washed with water (3 times), brine, and dried (MgSO4), filtered and concentrated. The crude product was purified on Biotage SP1 (40+M equilibrated), eluting with 20-80% ethyl acetate/hexanes, 20 CV (CV stands for column volume). LC/MS: [(M+1)]+=465.2;

1. customThe ice bath removed
2. customreaction mixture
3. customResulting mixture
4. concentrationwas then concentrated under reduced pressure
5. customResulting oil
6. stirringThe reaction mixture was stirred at room temperature under nitrogen for 2 hours
7. washwashed with water (3 times), brine
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude product was purified on Biotage SP1 (40+M equilibrated)
12. washeluting with 20-80% ethyl acetate/hexanes, 20 CV (CV stands for column volume)

ORD record

ord-c4227e84e7184e34955f2b3556ee5a78

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09206199B2