Hexane → tert-butyl 4-((1R,2R)-2-(((3-fluoro-4-(methylthio)benzyl)oxy)methyl)cyclopropyl)piperidine-1-carboxylate

Temperature

-78 °C

tert-butyl 4-((1R,2R)-2-(((4-bromo-3-fluorobenzyl)oxy)methyl)cyclopropyl)piperidine-1-carboxylate (Step A product, 7.7 g, 17.4 mmol) was dissolved in Diethyl ether (70 ml) and cooled to −78° C. The mixture was stirred for 5 min, then n-Butyllithium in hexane (2.5 M, 7.66 ml, 19.15 mmol) was added dropwise. The mixture was stirred at −78° C. for 10 min and dimethyl disulfide (1.85 ml, 20.9 mmol) was added dropwise. The mixture was stirred at −78° C. for 30 min and TLC showed the SM was almost consumed. The mixture was quenched with sat. NH4Cl at −78° C., extracted with EtOAc (2×). The EtOAc phase was washed with brine, dried over MgSO4, and concentrated to afford 7.13 g (100%) of the designed product. This crude product was used for the next step without further purification.

1. stirringThe mixture was stirred at −78° C. for 10 min
2. stirringThe mixture was stirred at −78° C. for 30 min
3. customwas almost consumed
4. customThe mixture was quenched with sat. NH4Cl at −78° C.
5. extractionextracted with EtOAc (2×)
6. washThe EtOAc phase was washed with brine
7. dry with materialdried over MgSO4
8. concentrationconcentrated

ORD record

ord-cb8ce691b0fa40658216ee8d806df246

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09006228B2