Potassium Carbonate → 4-{3-[4-(4-Cyanotetrahydropyran-4-yl)-phenoxy]propyl}-piperazine-1-carboxylic acid ethyl ester

HRID 272907Notes

Reaction equation

HRID 272907 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([C:22]#[N:23])[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.[CH2:24]([O:26][C:27]([N:29]1CCN(CCCCl)CC1)=[O:28])[CH3:25].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH2:24]([O:26][C:27]([N:29]1[CH2:4][CH2:5][N:1]([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([C:22]#[N:23])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:2][CH2:3]1)=[O:28])[CH3:25]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 410641Ethyl 4-(3-chloropropyl)piperazine-1-carboxylateHCID 598373944-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbonitrile

Product 1

HCID 598374324-{3-[4-(4-Cyanotetrahydropyran-4-yl)-phenoxy]propyl}-piperazine-1-carboxylic acid ethyl esterYield 28.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbonitrile (500 mg, 2.46 mmol), 4-(3-chloro-propyl)-piperazine-1-carboxylic acid ethyl ester (570 mg, 2.43 mmol), DMF (10 ml) and K2CO3 (1.36 g, 9.84 mmol) were reacted together according to general procedure E. The organic phase was washed with 2M NaOH (3.×20 ml), water (2×20 ml), dried over MgSO4, fitered and concentrated in vacuo at 35° C. The crude product was subjected to chromatography on silica eluting with DCM:MeOH:NH3 (97:2:1) to provide the title compound (280 mg, 28%) as an off white solid. 1H NMR (400 MHz, CDCl3), δ 7.38 (d, 2H), 6.93 (d, 2H), 4.14 (q, 2H), 4.11-4.05 (m, 2H), 4.03 (t, 2H), 3.89 (td, 2H), 3.55-3.42 (m, 4H), 2.53 (t, 2H), 2.47-2.36 (m, 4H), 2.15-1.92 (m, 6H), 1.26 (t, 3H).

Workup

  1. washThe organic phase was washed with 2M NaOH (3.×20 ml), water (2×20 ml)
  2. dry with materialdried over MgSO4
  3. concentrationfitered and concentrated in vacuo at 35° C

Sources & evidence

ORD record
ord-949bc005ee6341299f87ca3274f6fede
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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