Cesium carbonate → tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate

HRID 389446Notes

Reaction equation

CS(O[CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)(=O)=O.[CH3:19][C:20]1([CH3:32])[C:24]([CH3:26])([CH3:25])[O:23][B:22]([C:27]2[CH:28]=[N:29][NH:30][CH:31]=2)[O:21]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O>[CH3:19][C:20]1([CH3:32])[C:24]([CH3:25])([CH3:26])[O:23][B:22]([C:27]2[CH:31]=[N:30][N:29]([CH:6]3[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]3)[CH:28]=2)[O:21]1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of tert-butyl 4-[(methylsulfonyl)oxy]piperidine-1-carboxylate (7.33 g, 26.2 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (5.09 g, 26.2 mmol), and Cs2CO3 (12.8 g, 39.3 mmol) in DMF (50 mL) was heated at 100° C. for 24 h. The mixture was cooled to RT and diluted with water (100 mL) and extracted with EtOAc (3×60 mL). The combined organic phases were washed with water (3×50 mL), brine (50 mL), and dried over anhydrous sodium sulfate. The residue was purified by flash chromatography (20 to 40% ethyl acetate:hexanes) to afford 3.84 g (39%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 7.81 (s, 1H), 7.74 (s, 1H), 4.17-4.35 (m, 3H), 2.89 (m, J=11.12 Hz, 2H), 2.14 (d, J=14.65 Hz, 2H), 1.90 (qd, J=12.25, 4.42 Hz, 3H), 1.48 (s, 9H), 1.33 (s, 12H); MS (ESI): 379.15 [M+H]+; HPLC tR=3.17 min.

Workup

temperatureThe mixture was cooled to RT
extractionextracted with EtOAc (3×60 mL)
washThe combined organic phases were washed with water (3×50 mL), brine (50 mL)
dry with materialdried over anhydrous sodium sulfate
customThe residue was purified by flash chromatography (20 to 40% ethyl acetate:hexanes)

Sources & evidence

ORD record: ord-d4d3ca8674a6455c9a0be8e194b9d4d9
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08378104B2

Reaction notes

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