3,5-Dibromopyridine → Tert-butyl 4-(5-bromopyridin-3-yl)piperazine-1-carboxylate

HRID 2307793Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].CC(C)([O-])C.[Na+]>O1CCOCC1.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:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:2]2[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

Conditions

Temperature: 95 °C

Procedure

A solution of the 3,5-dibromo-pyridine (12.8 g, 68.8 mmol) and piperazine-1-carboxylic acid tert butyl ester (10 g, 42.4 mmol) in 200 mL of dioxane was treated with Pd2(dba)3 (5 g, 5.5 mmol), 2-(di-tbutyl-phosphino)biphenyl (4 g, 13.4 mmol), and sodium t-butoxide (7.2 g, 75 mmol). The reaction was heated to 95° C. for 8 h then cooled and filtered through celite. The mixture was evaporated and the residue was purified by flash column chromatography on silica gel, eluting with a solvent gradient of 1:4 ethyl acetate/hexane to 100% ethyl acetate. Recovered 2.9 g of product (20%). MS (ESI) m/z 344 (M+H)+.

Workup

temperaturethen cooled
filtrationfiltered through celite
customThe mixture was evaporated
customthe residue was purified by flash column chromatography on silica gel
washeluting with a solvent gradient of 1:4 ethyl acetate/hexane to 100% ethyl acetate
customRecovered 2.9 g of product (20%)

Sources & evidence

ORD record: ord-b0ab05137684442bb98b6abe41667324
Source dataset: uspto-grants-2004_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06831175B2

Reaction notes

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