Piperazine → 1-(6-Fluoronaphthalen-2-yl)piperazine

HRID 1772196Notes

Reaction equation

HRID 1772196 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([F:12])[CH:8]=2)[CH:3]=1.CC(C)([O-])C.[Na+].[NH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.C(Cl)(Cl)Cl>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].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[F:12][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[CH:3]=[C:2]([N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)[CH:11]=[CH:10]2

Participants

8

Reactant 4

HCID 4837PiperazineHCID 6212ChloroformHCID 3453972-Bromo-6-fluoronaphthaleneHCID 23676156Sodium t-butoxide

Product 1

HCID 867194671-(6-Fluoronaphthalen-2-yl)piperazineYield 73.4%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 2-bromo-6-fluoronaphthalene (1 g, 4.44 mmol) in 30 ml of toluene was added sodium tert-butoxide (0.854 g, 8.89 mmol, 2.0 eq), piperazine (0.764 g, 8.87 mmol, 2.0 eq), BINAP (28 mg, 0.045 mmol, 1 mol %) and Pd2(dba)3.CHCl3 (92 mg, 0.089 mmol, 2 mol %) at 70° C. in an oil bath under an inert atmosphere of nitrogen. The resulting solution was stirred overnight and then concentrated under vacuum. The crude material was purified by silica gel chromatography using 10-20% methanol in dichloromethane to elute. The product-containing fractions were combined and concentrated under vacuum to afford 1-(6-fluoronaphthalen-2-yl)piperazine as a light yellow solid (0.75 g, 73%). (ES, m/z): [M+H]+ 231.1; 1H NMR (300 MHz, CDCl3): δ 7.67-7.73 (m, 2H), 7.29-7.38 (m, 2H), 7.18-7.23 (m, 1H), 7.14 (d, J=1.8 Hz, 1H), 3.24 (dd, J=3.6, 3.9 Hz, 4H), 3.12 (dd, J=3.6, 3.9 Hz, 4H).

Workup

  1. customat 70° C.
  2. concentrationconcentrated under vacuum
  3. customThe crude material was purified by silica gel chromatography
  4. washto elute
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-23f0a1e5b36541b7a993bd1363c160a5
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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