2-Tetralone → [3-(4-Methyl-piperazin-1-yl)-propyl]-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amine

HRID 1986625Notes

Reaction equation

HRID 1986625 reaction equation
[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][C:2]1=O.[NH2:12][CH2:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]1.[BH4-].[Na+]>CO.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH3:22][N:19]1[CH2:20][CH2:21][N:16]([CH2:15][CH2:14][CH2:13][NH:12][CH:2]2[CH2:3][CH2:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH2:1]2)[CH2:17][CH2:18]1

Participants

6

Reactant 3

HCID 682662-TetraloneHCID 783281-(3-Aminopropyl)-4-methylpiperazineHCID 4311764Sodium borohydride

Product 1

HCID 43225477[3-(4-Methyl-piperazin-1-yl)-propyl]-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amineYield 67%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

A neat mixture of 2-tetralone (0.552 g, 3.78 mmol), 1-(3-aminopropyl)-4-methylpiperazine (0.713 g, 4.54 mmol, 1.2 eq), and titanium (IV) isopropoxide (1.44 g, 5.67 mmol, 1.5 eq) was heated at 80° C. for 3 hours. The mixture was cooled to 0° C., diluted with 5 mL of MeOH, and then treated with NaBH4 (0.143 g, 3.78 mmol, 1 eq, adding portionwise). The resulting mixture was stirred at 0° C. for 30 min and then at room temperature for 12 hours. The reaction mixture was concentrated in vacuo, treated with water (3 mL) and then MeOH (30 mL), filtered through Celite. The filtrate was concentrated in vacuo, and the residue was redissolved in water (25 mL) and extracted with CHCl3 (3×25 mL). The combined CHCl3 extracts were dried (MgSO4) and concentrated to give [3-(4-methyl-piperazin-1-yl)-propyl]-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amine as a dark brown oil (0.721 g, 67%). The crude intermediate was used in the subsequent step without further purification.

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. additionadding portionwise)
  3. waitat room temperature for 12 hours
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. additiontreated with water (3 mL)
  6. filtrationMeOH (30 mL), filtered through Celite
  7. concentrationThe filtrate was concentrated in vacuo
  8. dissolutionthe residue was redissolved in water (25 mL)
  9. extractionextracted with CHCl3 (3×25 mL)
  10. dry with materialThe combined CHCl3 extracts were dried (MgSO4)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-2c99630b50144273a3ebb59877440742
Source dataset
uspto-grants-2009_06
Patent number
US07550467B2

Reaction notes

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