1-Methylpiperazine → 1-Methyl-4-{4-[4-(3-pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-piperazine

HRID 272868Notes

Reaction equation

HRID 272868 reaction equation
[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH:22]=O)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:24][N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(O)C>[CH3:24][N:25]1[CH2:30][CH2:29][N:28]([CH2:22][C:16]2([C:13]3[CH:12]=[CH:11][C:10]([O:9][CH2:8][CH2:7][CH2:6][N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:15][CH:14]=3)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[CH2:27][CH2:26]1

Participants

5

Reactant 2

HCID 531671-MethylpiperazineHCID 598374274-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbaldehyde

Product 1

HCID 117110931-Methyl-4-{4-[4-(3-pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-piperazineYield 56.7%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolvent

Procedure

A solution of 4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbaldehyde (500 mg, 1.58 mmol, 1 wt), 1-methylpiperazine (300 mg, 2.99 mmol), absolute ethanol (20 ml, 40 vol), activated 3 Å molecular sieves (500 mg), titanium (IV) isopropoxide (2.32 ml, 7.83 mmol) and STAB (1.43 g, 6.73 mmol) were reacted in accordance with the general procedure D. The isolated oil was purified by column chromatography on silica (20 g, 28.6 wt) eluting with DCM(95):MeOH(4):NH3(I) to give the title compound as a clear viscous oil (360 mg, 56%). 1H NMR (400 MHz, CDCl3) δ7.21 (d, 2H), 6.86 (d, 2H), 4.02 (t, 2H), 3.75 (dt2H), 3.60-3.47 (m, 2H), 2.63 (t, 2H), 2.53 (br s, 4H), 2.38 (s, 2H), 2.34-2.14 (m, 11H), 2.13-1.73 (m, 10H).

Workup

  1. customThe isolated oil was purified by column chromatography on silica (20 g, 28.6 wt)
  2. washeluting with DCM(95)

Sources & evidence

ORD record
ord-7151cbdc696343db9c2d0a404d5e4d8d
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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