Hydrochloric Acid → HCID 60037921, compound

HRID 1793439Notes

Reaction equation

HRID 1793439 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C@H:11]([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[CH3:12])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].Br[C:20]1[CH:21]=[CH:22][C:23]([Cl:28])=[C:24]([O:26][CH3:27])[CH:25]=1.CC(C)([O-])C.[K+].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]>[Cl:28][C:23]1[CH:22]=[CH:21][C:20]([N:16]2[CH2:15][CH2:14][N:13]([C@@H:11]([C:5]3[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=3)[CH3:12])[CH2:18][CH2:17]2)=[CH:25][C:24]=1[O:26][CH3:27]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 27695675-Bromo-2-chloroanisoleHCID 23665647Potassium tert-butoxideHCID 28798624HCID 28798624, compound

Product 1

HCID 60037921HCID 60037921, compoundYield 61.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A quantity of 4.2 g (17 mmoles, 1 eq) of (R)-1-[1-(3,4-dimethoxy-phenyl)-ethyl]-piperazine and 4.4 g (20 mmoles, 1.2 eq) of 5-Bromo-2-chloro-anisole was dissolved in 110 mL of anhydrous toluene, and the solution is purged with N2 for 20 minutes. To the solution was added 0.33 g (0.5 mmoles, 0.03 eq) of rac-2, 2′-Bis(diphenyl-phosphino)-1,1′-binapphtyl, 0.031 g (0.34 mmole, 0.02 eq) of tris(dibenzylideneacetone)-dipalladium(0) and 2.4 g (22 mmoles, 1.3 eq) of potassium tert-butoxide in order. The mixture was heated at 80° C. under N2 overnight. After cooled down, the reaction was filtered through Celite. The organic solution is washed with 1N NaOH and brine, dried over Na2SO4 and concentrated. The residue was purified by flash chromatography on silica gel eluted with 1:1 ethyl acetate: hexanes to afford brownish oil. The product (compound 4) was converted to its HCl salt, giving yellowish solid (4.1 g, 53%). Mp: 172–6° C. Analysis: 1H NMR (300 MHz, DMSO): 11.8 (1H, s), 9.2 (1H, s), 7.48 (1H, s), 7.21(1H, d), 7.12 (1H, dd), 6.99 (1H, d), 6.68 (1h, d), 6.59 (1H, dd), 4.42 (1H, t), 3.80 (12H, m), 3.39 (1H, t), 3.19 (1H, t), 2.99 (3H, m), 1.73 (3H, d). MS (LC-MS): Calculated for C21H27ClN2O3 390.90, found 391.38 (M+).

Workup

  1. customthe solution is purged with N2 for 20 minutes
  2. temperatureAfter cooled down
  3. filtrationthe reaction was filtered through Celite
  4. washThe organic solution is washed with 1N NaOH and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography on silica gel
  8. washeluted with 1:1 ethyl acetate
  9. customhexanes to afford brownish oil

Sources & evidence

ORD record
ord-e708439672104902ad9652f8c150d57e
Source dataset
uspto-grants-2006_07
Patent number
US07081458B2

Reaction notes

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