1-Bromo-4-fluorobenzene → HCID 89924447, compound

HRID 2200352Notes

Reaction equation

HRID 2200352 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][C:9]1([CH3:15])[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>O1CCOCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH2:10][C:9]1([CH3:15])[CH3:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 99931-Bromo-4-fluorobenzeneHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 509875782,2-Dimethyl-1-(phenylmethyl)piperazine

Product 1

HCID 89924447HCID 89924447, compoundYield 62.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 1-benzyl-2,2-dimethylpiperazine (1.2 g, 5.87 mmol) in 1,4-dioxane (50 ml) at 25° C. was added 1-bromo-4-fluorobenzene (1.233 g, 7.05 mmol), 2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) (0.366 g, 0.587 mmol), sodium tert-butoxide (1.129 g, 11.75 mmol), and tris(dibenzyllideneacetone)dipalladium (0) [Pd2(dba)3] (0.269 g, 0.294 mmol). The reaction mixture was purged with nitrogen for 10 min in sealed tube and then heated at 100° C. for 5 h. The progress of reaction was monitored by TLC. The reaction mixture was cooled to 25° C., filtered through celite, washed with ethyl acetate (2×50 ml). The combined filtrate was concentrated under reduced pressure to obtain a crude product. The crude product was purified over silica gel (100-200 mesh) by flash chromatography using 10% ethyl acetate in hexane as eluent to obtain the title compound (1.1 g, 62.8%)

Workup

  1. customThe reaction mixture was purged with nitrogen for 10 min in sealed tube
  2. customThe progress of reaction
  3. temperatureThe reaction mixture was cooled to 25° C.
  4. filtrationfiltered through celite
  5. washwashed with ethyl acetate (2×50 ml)
  6. concentrationThe combined filtrate was concentrated under reduced pressure
  7. customto obtain a crude product
  8. customThe crude product was purified over silica gel (100-200 mesh) by flash chromatography

Sources & evidence

ORD record
ord-d32d2beb0daa4ea88de7a1a60cb15a37
Source dataset
uspto-grants-2016_06
Patent number
US09359367B2

Reaction notes

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