5-Bromo-2-fluoropyridine → 1-Tert-butyl-4-(6-fluoropyridin-3-yl)piperazine

HRID 40703

Reaction equation

[C:1]([N:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].Br[C:12]1[CH:13]=[CH:14][C:15]([F:18])=[N:16][CH:17]=1.CC(C)([O-])C.[Na+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C>[C:1]([N:5]1[CH2:10][CH2:9][N:8]([C:12]2[CH:17]=[N:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

1-tert-Butylpiperazine (1.61 g, 11.4 mmol) is placed in 35 ml of toluene under nitrogen, 5-Bromo-2-fluoropyridine (2 g, 11.4 mmol), sodium t-butoxide (1.6 g, 17 mmol), tris(dibenzylideneacetone)dipalladium (0.52 g, 0.57 mmol), and S-Phos (0.93 g, 17 mmol) are then added. The reaction medium is heated at 80° C. for 18 h. After hydrolysis, and extraction with ethyl acetate, the organic phase is washed with water and then with a saturated aqueous sodium chloride solution. After drying over MgSO4, and concentrating to dryness, the crude product obtained is chromatographed on silica gel, elution being carried out with a gradient of methanol in dichloromethane ranging from 0% to 5%. 1.92 g of 1-tert-butyl-4-(6-fluoropyridin-3-yl)piperazine are obtained.

Workup

washthe organic phase is washed with water
dry with materialAfter drying over MgSO4
concentrationconcentrating to dryness
customthe crude product obtained
customis chromatographed on silica gel, elution

Sources & evidence

ORD record: ord-1415b2b69aab4cb587315c27bb5ff3fe
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530477B2

Linked notes

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