Cesium carbonate → Tert-butyl 4-(5-chloro-3-(methoxycarbonyl)-2-methylphenoxy)piperidine-1-carboxylate

HRID 1050446Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([OH:13])[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].CS(O[CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[Cl:1][C:2]1[CH:11]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[C:5]([CH3:12])=[C:4]([CH:3]=1)[O:13][CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1

Participants

Conditions

Temperature: 75 °C

Procedure

A mixture of methyl 5-chloro-3-hydroxy-2-methylbenzoate (1.25 g, 6.23 mmol), tert-butyl 4-((methylsulfonyl)oxy)piperidine-1-carboxylate (3.66 g, 13.08 mmol) and cesium carbonate (5.08 g, 15.58 mmol) in DMF (25 mL) was heated at 75° C. for 18 h. The reaction was allowed to cool to ambient temperature and poured into ice/water (200 mL) with stirring. The mixture was extracted with EtOAc (3×100 mL), dried over magnesium sulfate, and concentrated in vacuo. The light yellow residue was purified by flash chromatography (5-50% EtOAc/hexanes) to give tert-butyl 4-(5-chloro-3-(methoxycarbonyl)-2-methylphenoxy)piperidine-1-carboxylate (1.95 g, 5.08 mmol, 82% yield) as a solid. 1H NMR (DMSO-d6) δ 7.37 (d, J=2.0 Hz, 1H), 7.31 (d, J=2.0 Hz, 1H), 4.71 (dt, J=7.4, 3.8 Hz, 1H), 3.83 (s, 3H), 3.54-3.63 (m, 2H), 3.22-3.31 (m, 2H), 2.28 (s, 3H), 1.83-1.93 (m, 2H), 1.51-1.63 (m, 2H), 1.41 (s, 9H).

Workup

temperatureto cool to ambient temperature
extractionThe mixture was extracted with EtOAc (3×100 mL)
dry with materialdried over magnesium sulfate
concentrationconcentrated in vacuo
customThe light yellow residue was purified by flash chromatography (5-50% EtOAc/hexanes)

Sources & evidence

ORD record: ord-897c79457deb412a8f02afb365e546ed
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382234B2

Reaction notes

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