Potassium Carbonate → 4-{3-[4-(4-Cyano-tetrahydro-pyran-4-yl)-phenoxy]-propyl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 272908Notes

Reaction equation

HRID 272908 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.[C:24]([O:28][C:29]([N:31]1CCN(CCCCl)CC1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:24]([O:28][C:29]([N:31]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:30])([CH3:27])([CH3:26])[CH3:25]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 53412057tert-Butyl 4-(3-chloropropyl)piperazine-1-carboxylateHCID 598373944-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbonitrile

Product 1

HCID 598375064-{3-[4-(4-Cyano-tetrahydro-pyran-4-yl)-phenoxy]-propyl}-piperazine-1-carboxylic acid tert-butyl esterYield 83.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbonitrile (200 mg, 0.99 mmol), 4-(3-chloro-propyl)-piperazine-1-carboxylic acid tert-butyl ester (203 mg, 0.76 mmol), DMF (4 ml) and K2CO3 (553 g, 4.00 mmol) was heated to 70° C. and work up 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 concentrate in vacuo at 35° C. to provided the title compound (272 mg, 64%) as an off white solid. 1H NMR (400 MHz, CDCl3), δ 7.38 (d, 2H), 6.93 (d, 2H), 4.11-4.04 (m, 2H), 4.03 (t, 2H), 3.89 (td, 2H), 3.50-3.37 (m, 4H), 2.53 (t, 2H), 2.45-2.34 (m, 4H), 2.15-2.00 (m, 4H), 1.97 (p, 2H), 1.46 (s, 9H).

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 concentrate in vacuo at 35° C.

Sources & evidence

ORD record
ord-8483cf3b1094408e9bba24aa1eada4dd
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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