Hydrochloric Acid → HCID 86719340, compound

HRID 922357Notes

Reaction equation

HRID 922357 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:10]2[O:15]CCCO2)[CH:5]=[C:6]([O:8][CH3:9])[CH:7]=1.[CH:16]([N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)([CH3:18])[CH3:17].CC(C)([O-])C.[Na+].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.Cl.[OH-].[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]>[CH:16]([N:19]1[CH2:24][CH2:23][N:22]([C:2]2[CH:3]=[C:4]([CH:5]=[C:6]([O:8][CH3:9])[CH:7]=2)[CH:10]=[O:15])[CH2:21][CH2:20]1)([CH3:18])[CH3:17]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 780131-IsopropylpiperazineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 86719339HCID 86719339, compound

Product 1

HCID 86719340HCID 86719340, compoundYield 27.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-(3-bromo-5-methoxyphenyl)-1,3-dioxane (4.75 g, 17.4 mmol), 1-isopropyl-piperazine (3.14 mL, 21.96 mmol), sodium-tert-butoxide (3.00 g, 31.3 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.342 g, 0.55 mmol) and tris(dibenzylideneacetone)dipalladium (0) (0.167 g, 0.18 mmol) in toluene (40 mL) was stirred at 100° C. for 18 h. After this time the reaction was cooled to rt and the dark brown mixture was poured into an ice-cold solution of 1N HCl (100 mL) and stirred vigorously for 2 h at rt. After this time the reaction mixture was re-cooled to 0° C. and the pH was adjusted to 13 with 6N NaOH solution. The reaction mixture was then extracted with diethyl ether. The organic phase was concentrated, taken up in 2N HCl (50 mL) and stirred for 1 h. The resulting mixture was extracted with dichloromethane (2×150 mL). The pH of the aqueous phase was adjusted to approximately 13 with 6N NaOH solution and extracted with diethyl ether (2×150 mL). The combined organic phase was washed with water, dried over anhydrous Na2SO4, and concentrated under reduced pressure to give 3-(4-isopropylpiperazin-1-yl)-5-methoxybenzaldehyde (1.24 g, 27%) as a viscous red oil: 1H NMR (400 MHz, CDCl3): δ 9.90 (s, 1H), 7.05 (dd, J=2.15, 1.37 Hz, 1H), 6.88 (dd, J=1.95, 1.17 Hz, 1H), 6.69 (t, J=2.34 Hz, 1H), 3.85 (s, 3H), 3.25-3.28 (m, 4H), 2.64-2.78 (m, 5H), 1.10 (d, J=6.64 Hz, 6H).

Workup

  1. temperatureAfter this time the reaction was cooled to rt
  2. stirringstirred vigorously for 2 h at rt
  3. temperatureAfter this time the reaction mixture was re-cooled to 0° C.
  4. extractionThe reaction mixture was then extracted with diethyl ether
  5. concentrationThe organic phase was concentrated
  6. stirringstirred for 1 h
  7. extractionThe resulting mixture was extracted with dichloromethane (2×150 mL)
  8. extractionextracted with diethyl ether (2×150 mL)
  9. washThe combined organic phase was washed with water
  10. dry with materialdried over anhydrous Na2SO4
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cea8204fad3244c5aafc373b2697e1a5
Source dataset
uspto-grants-2016_03
Patent number
US09278940B2

Reaction notes

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