Hexane → tert-butyl 4-((1R,2R)-2-(((3-fluoro-4-(methylthio)benzyl)oxy)methyl)cyclopropyl)piperidine-1-carboxylate
Reaction equation
Br[C:2]1[CH:26]=[CH:25][C:5]([CH2:6][O:7][CH2:8][C@@H:9]2[CH2:11][C@@H:10]2[CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)=[CH:4][C:3]=1[F:27].C([Li])CCC.CCCCCC.[CH3:39][S:40]SC>C(OCC)C>[F:27][C:3]1[CH:4]=[C:5]([CH:25]=[CH:26][C:2]=1[S:40][CH3:39])[CH2:6][O:7][CH2:8][C@@H:9]1[CH2:11][C@@H:10]1[CH:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
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.
Workup
- stirringThe mixture was stirred at −78° C. for 10 min
- stirringThe mixture was stirred at −78° C. for 30 min
- customwas almost consumed
- customThe mixture was quenched with sat. NH4Cl at −78° C.
- extractionextracted with EtOAc (2×)
- washThe EtOAc phase was washed with brine
- dry with materialdried over MgSO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-cb8ce691b0fa40658216ee8d806df246
- Source dataset
- uspto-grants-2015_04
- Patent number
- US09006228B2
Reaction notes
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