Water → BOC-4-((S)-2-Methyl-pyrrolidin-1-yl)piperidine

HRID 2401099Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11](OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:25][C@H:26]1[CH2:30][CH2:29][CH2:28][NH:27]1.C([O-])([O-])=O.[K+].[K+].O>C(#N)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:27]2[CH2:28][CH2:29][CH2:30][C@@H:26]2[CH3:25])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 4-(toluene-4-sulfonyloxy)-piperidine-1-carboxylic acid tert-butyl ester (8.1 g, 22.8 mmol), (S)-(+)-2-methylpyrrolidine (2.33 g, 27.36 mmol), K2CO3 (6.93 g, 50.16 mmol) in acetonitrile (76 mL) was heated to 80° C. for 20 h and then added additional (S)-(+)-2-methylpyrrolidine (834 mg, 9.79 mmol), and the temperature of the reaction mixture was maintained at 80° C. for 20 h. The heating was removed and the solution was concentrated to provide a residue which was taken up with H2O (100 mL) and extracted with CH2Cl2 (2×100 mL). The organic layers were dried over K2CO3, filtered and concentrated to provide a crude oil which was purified by flash column chromatography (0 to 5% MeOH/CH2Cl2) to provide 2.43 g (40% yield) of the title compound as a solid.

Workup

customThe heating was removed
concentrationthe solution was concentrated
customto provide a residue which
extractionextracted with CH2Cl2 (2×100 mL)
dry with materialThe organic layers were dried over K2CO3
filtrationfiltered
concentrationconcentrated
customto provide a crude oil which
customwas purified by flash column chromatography (0 to 5% MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-5712522f406e44f0a0c94d3bc967db34
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08796278B2

Reaction notes

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