1-Piperazinecarboxylic acid, ethyl ester → HCID 59837364, compound

HRID 272875Notes

Reaction equation

HRID 272875 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.[N:24]1([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(O)C>[CH2:33]([O:32][C:30]([N:24]1[CH2:25][CH2:26][N:27]([CH2:22][C:16]2([C:13]3[CH:14]=[CH:15][C:10]([O:9][CH2:8][CH2:7][CH2:6][N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:11][CH:12]=3)[CH2:17][CH2:18][O:19][CH2:20][CH2:21]2)[CH2:28][CH2:29]1)=[O:31])[CH3:34]

Participants

5

Reactant 2

HCID 84311-Piperazinecarboxylic acid, ethyl esterHCID 598374274-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbaldehyde

Product 1

HCID 59837364HCID 59837364, compound

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolvent

Procedure

4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbaldehyde (500 mg, 1.58 mmol), ethyl piperazine-1-carboxylate (471 mg, 3.00 mmol), absolute ethanol (20 ml), activated 3 Å molecular sieves (500 mg), titanium (IV) isopropoxide (2.31 ml, 7.88 mmol) and STAB (2.84 g, 13.6 mmol) were reacted in accordance with the general procedure D. The isolated crude product was purified by column chromatography on silica eluting with DCM:MeOH:NH3 (97:2:1) to give the title compound as a white solid containing residual 4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbaldehyde (350 mg). The material was dissolved in DCM (14 ml) and PS-AMPS (loading 2.04 mmol-1 g, 23 mg) was added and shaken for 24 hours. The resin was filtered and the solution concentrated in vacuo at 30° C., the crude material was subjected to chromatography on silica eluting with DCM:MeOH:NH3 (97:2:1) to give the title compound as a white solid (130 mg, 18%). 1H NMR (400 MHz, CDCl3) δ 7.20 (d, 2H), 6.86 (d, 2H), 4.08 (q, 2H), 4.02 (t, 2H), 3.79-3.70 (m, 2H), 3.57-3.47 (m, 2H), 3.27 (br s, 4H), 2.63 (t, 2H), 2.53 (br s, 4H), 2.38 (s, 2H), 2.21-1.73 (m, 14H), 1.21 (t, 3H).

Workup

  1. customThe isolated crude product
  2. customwas purified by column chromatography on silica eluting with DCM:MeOH:NH3 (97:2:1)

Sources & evidence

ORD record
ord-dd59219225fb4c0da1889875da95f022
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

Loading…