Cesium carbonate → Tert-butyl 4-(6-fluoropyridin-3-yl)piperazine-1-carboxylate

HRID 271560

Reaction equation

Cl.[C:2]([O:6][C:7]([N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)=[O:8])([CH3:5])([CH3:4])[CH3:3].Br[C:16]1[CH:17]=[CH:18][C:19]([F:22])=[N:20][CH:21]=1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O.CCCCCC.O>[C:2]([O:6][C:7]([N:9]1[CH2:14][CH2:13][N:12]([C:16]2[CH:21]=[N:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH2:11][CH2:10]1)=[O:8])([CH3:5])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: 80 °C

Procedure

A suspension of piperazine-1-carboxylic acid tert-butyl ester hydrochloride (0.75 mmol), 5-bromo-2-fluoropyridine (0.90 mmol), (R)-2,2′-bis(diphenylphosphino)-1, 1′-binaphthyl (0.038 mmol), palladium acetate (0.038 mmol) and cesium carbonate (1.8 mmol) in toluene is stirred at 80° C. for 7 h and then 100° C. for 4 h, and poured into water. The mixture is extracted with AcOEt. The organic layer is washed with water, dried over magnesium sulfate, and concentrated. The crude product is purified by silica gel column chromatography to give the product in 43% yield. Rf=0.61 (n-hexane:AcOEt=1:1)

Workup

wait100° C. for 4 h
extractionThe mixture is extracted with AcOEt
washThe organic layer is washed with water
dry with materialdried over magnesium sulfate
concentrationconcentrated
customThe crude product is purified by silica gel column chromatography
customto give the product in 43% yield

Sources & evidence

ORD record: ord-61ffb66676194eb78c51d58eeeef3fb6
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07452886B2

Linked notes

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