tert-Butyl piperazine-1-carboxylate → Tert-butyl 4-(6-bromopyridin-3-yl)piperazine-1-carboxylate

HRID 2209274Notes

Reaction equation

HRID 2209274 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][N:3]=1.[N:9]1([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.CC([O-])(C)C.[Na+]>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]>[Br:1][C:2]1[N:3]=[CH:4][C:5]([N:12]2[CH2:11][CH2:10][N:9]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:14][CH2:13]2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 47382712-Bromo-5-iodopyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 11530243Tert-butyl 4-(6-bromopyridin-3-yl)piperazine-1-carboxylateYield 90.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Into the mixture solution of 2-bromo-5-iodopyridine (9.15 g, 32.2 mmol), tert-butyl piperazine-1-carboxylate (5 g, 27 mmol) in Toluene (90 mL) was added Tris(dibenzylideneacetone)dipalladium (0) (0.983 g, 1.1 mmol), 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (0.17 g, 3.2 mmol) and NaOtBu (7.8 g, 80.5 mmol). Then the reaction mixture was flushed with Argon and stirred for 2 h. The reaction mixture was extracted with ethyl acetate and washed with brine. After drying with MgSO4, the organic solvent was removed under vaco., the residue was purified by crystallization from mixture of DCM and Hexane to get 8.4 g of tert-butyl 4-(6-bromopyridin-3-yl)piperazine-1-carboxylate 7.13. 1H NMR (400 MHz, CDCl3) ppm: δ 8.01 (d, J=3.2 H2, 1H), 7.32 (d, J=8.4 Hz, 1H), 7.07 (d, d, J=3.2, 8.4 Hz, 1H), 3.59 (t, J=5.4 Hz, 4H), 3.237 (t, J=5.4 Hz, 4H), 1.478 (s, 9H).

Workup

  1. customThen the reaction mixture was flushed with Argon
  2. extractionThe reaction mixture was extracted with ethyl acetate
  3. washwashed with brine
  4. dry with materialAfter drying with MgSO4
  5. customthe organic solvent was removed under vaco
  6. custom, the residue was purified by crystallization from mixture of DCM and Hexane

Sources & evidence

ORD record
ord-69c63824c5b54fcb9f890121d62f38fb
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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