Cesium carbonate → tert-Butyl 6-[(1-methyl-1H-pyrazol-5-yl)amino]-4-oxo-spiro[chroman-2,4'-piperidine]-1'-carboxylate

HRID 1096931Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:21](=[CH:22][CH:23]=1)[O:20][C:7]1([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1)[CH2:6][C:5]2=[O:24].[NH2:25][C:26]1[N:30]([CH3:31])[N:29]=[CH:28][CH:27]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:31][N:30]1[C:26]([NH:25][C:2]2[CH:3]=[C:4]3[C:21](=[CH:22][CH:23]=2)[O:20][C:7]2([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[CH2:6][C:5]3=[O:24])=[CH:27][CH:28]=[N:29]1

Participants

Conditions

Temperature: 110 °C

Procedure

Tert-Butyl 6-bromo-4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (16.3 g), 5-amino-1-methyl-1H-pyrazole (4.00 g), palladium acetate (922 mg), 2-(di-t-butylphosphino)biphenyl (1.23 g) and cesium carbonate (16.1 g) were suspended in 1,4-dioxane (20 mL), and heated under reflux at 110° C. for 5 hours. The reaction liquid was filtered through Celite, the residue on the Celite was washed with chloroform, and the filtrate was concentrated under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane/EtOAc) to obtain the intended compound as a yellow amorphous solid.

Workup

temperatureheated
customThe reaction liquid
filtrationwas filtered through Celite
washthe residue on the Celite was washed with chloroform
concentrationthe filtrate was concentrated under reduced pressure
customThe resulting residue was purified through silica gel column chromatography (hexane/EtOAc)

Sources & evidence

ORD record: ord-e660982f62bc4a158a22815fb13ca6b7
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08138197B2

Reaction notes

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