Toluene → HCID 66938969, compound

HRID 1716898Notes

Reaction equation

HRID 1716898 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([Br:9])[CH:3]=1.[CH3:10][N:11]1[CH2:16][CH2:15][CH:14]([NH:17][CH3:18])[CH2:13][CH2:12]1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>C(OCC)(=O)C.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].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>[CH3:10][N:11]1[CH2:16][CH2:15][CH:14]([NH:17][CH2:18][C:2]2[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([Br:9])[CH:3]=2)[CH2:13][CH2:12]1

Participants

8

Reactant 4

HCID 1140TolueneHCID 1370031,3-Dibromo-5-fluorobenzeneHCID 5663231-Methyl-4-(methylamino)piperidineHCID 23676156Sodium t-butoxide

Product 1

HCID 66938969HCID 66938969, compoundYield 55.3%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Combine 1,3-dibromo-5-fluorobenzene (5.0 g, 19.7 mmol), 1-methyl-4-(methylamino)piperidine (2.58 mL, 17.7 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.49 g, 0.79 mmol), sodium t-butoxide (2.57 g, 27.58 mmol) and toluene (100 mL), stir and heat at 80° C. After 10 minutes, add Pd2(dba)3 (0.49 g, 0.79 mmol). After 3 hr. at 80° C., cool to ambient temperature. Dilute with ethyl acetate (100 mL) and wash with water (50 mL). Dry the organic layer over sodium sulfate, filter, and concentrate to an oil. Purify the residue by silica gel flash chromatography eluting with 10% (2M NH3-methanol) in CH2Cl2 to obtain 2.95 g (55%) of the title intermediate: 1H NMR (CDCl3): 6.6 (s, 1H), 6.5 (m, 1H), 6.3 (m, 1H), 3.5 (m, 1H), 2.9 (m, 2H), 2.7 (s, 3H), 2.3 (s, 3H), 2.0 (m, 2H), 1.8 (m, 2H), 1.7 (m, 2H).

Workup

  1. waitAfter 3 hr
  2. temperatureat 80° C., cool to ambient temperature
  3. washwash with water (50 mL)
  4. dry with materialDry the organic layer over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate to an oil
  7. customPurify the residue by silica gel flash chromatography
  8. washeluting with 10% (2M NH3-methanol) in CH2Cl2

Sources & evidence

ORD record
ord-e0cdeabaa9e844079673c1c1a70c7683
Source dataset
uspto-grants-2010_09
Patent number
US07803813B2

Reaction notes

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