Cesium carbonate → tert-Butyl 4-((2-chloropyrimidin-4-yl)oxy)piperidine-1-carboxylate

HRID 1028130Notes

Reaction equation

[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[Cl:15][C:16]1[N:21]=[C:20](Cl)[CH:19]=[CH:18][N:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C(OCC)(=O)C>[Cl:15][C:16]1[N:21]=[C:20]([O:1][CH:2]2[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]2)[CH:19]=[CH:18][N:17]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To tert-butyl 4-hydroxypiperidine-1-carboxylate (389 mg, 1.933 mmol) and 2,4-dichloropyrimidine (240 mg, 1.611 mmol) in N,N-dimethylformamide (6.4 mL) was added cesium carbonate (1050 mg, 3.22 mmol) and the mixture was heated at 80° C. for 1 hour and then to 70° C. overnight. The reaction was then cooled to ambient temperature, diluted with ethyl acetate, and washed with water (3×) and brine (1×). The organic layer was dried, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (0-50% ethyl acetate/hexanes) to provide 410 mg (1.3 mmol, 81%) of tert-butyl 4-[(2-chloropyrimidin-4-yl)oxy]piperidine-1-carboxylate as white solid. MS APCI: [M+H]+ m/z 314.2.

Workup

customto 70° C.
customovernight
temperatureThe reaction was then cooled to ambient temperature
washwashed with water (3×) and brine (1×)
customThe organic layer was dried
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by column chromatography on silica gel (0-50% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-86d426f869de47c78e8ea9cb1838ce7f
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08735417B2

Reaction notes

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