N-(2-Methoxyphenyl)piperazine hydrochloride → 1-(2-Methoxyphenyl)piperazine

HRID 890996Notes

Reaction equation

HRID 890996 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1>O>[CH3:2][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1

Participants

3

Reactant 1

HCID 9899402N-(2-Methoxyphenyl)piperazine hydrochloride

Product 1

HCID 13461-(2-Methoxyphenyl)piperazineYield 96%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 25.00 g (0.1093 mol) of 1-(2′-methoxyphenyl)piperazine hydrochloride in 42 mL of water was added 14.5 mL (0.109 mol) of concentrated (29.4%) NH4OH (aq) (pH=9). The mixture was extracted twice with 250 mL of 1:1 (v/v) of THF:toluene. The organic extracts were combined, dried over MgSO4, gravity filtered and concentrated to afford 20.17 g (96.00%) of 1-(2′-methoxyphenyl)piperazine as a pale green oil: 1H NMR (d6-DMSO): d 6.90-6.97 (m, 2H, phenyl CH), 6.83-6.90 (m, 3H, phenyl CH), 3.77 (s, 3H, OCH3), 2.77-2.91 (m, 8H, piperazine CH2), 2.49-2.53 (m, 1H, NH). A solution of 9.55 g (0.0370 mol) of 4-cyclohexyl-3-methyl-4-oxo-3-phenylbutyraldehyde in 10 mL of iPrOAc was added to 6.77 g (0.0352 mol) of neat 1-(2′-methoxyphenyl)piperazine. The mixture turned turbid, and then turned to a solid mass when 10 mL of iPrOAc was added. The solid was slurried with 45 mL of iPrOAc. After 1.5 h, reaction was complete. The solid was vacuum filtered and washed with 10 mL of iPrOAc and air dried to afford 9.81 g (64.4%) of pure enamine as an off-white powder. The filtrate was concentrated to afford 6.40 g of crude enamine; 1H NMR (d6-DMSO): δ 7.31-7.43 (m, 2H, phenyl CH), 7.20-7.31 (m, 3H, phenyl CH), 6.82-7.04 (m, 4H, phenyl CH), 6.06 (d, J=14.2 Hz, 1H, CR3CH═CHNR2(trans)), 4.98 (d, J=14.2 Hz, 1H, CR3CH═CHNR 2(trans)), 3.80 (s, 3H, OCH3), 2.93-3.15 (m, 8H, piperazine CH2), 2.38-2.49 (m, 1H, cyclohexyl CH), 1.59-1.72 (m, 2H, cyclohexyl CH2), 1.47-1.59 (m, 2H, cyclohexyl —CH2), 1.40 (s, 3H, R2C(CH3)Ph), 1.21-1.34 (m, 3H, cyclohexyl —CH2), 1.03-1.21 (m, 2H, cyclohexyl —CH2), 0.83-1.03 (m, 1H, cyclohexyl —CH2).

Workup

  1. concentrationof concentrated (29.4%) NH4OH (aq) (pH=9)
  2. extractionThe mixture was extracted twice with 250 mL of 1:1 (v/v) of THF
  3. dry with materialdried over MgSO4, gravity
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-fec53933fe6942cca21fccbf23688610
Source dataset
uspto-grants-2006_02
Patent number
US07001908B2

Reaction notes

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