Acetic Acid → 4-[4-[(2S)-2-Hydroxy-3-(2-oxo-2,3-dihydro-1H-benzoimidazole-4-yloxy)-propylamino]-piperidin--1-yl}-benzoic acid ethyl ester

HRID 1061308Notes

Reaction equation

HRID 1061308 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]2)=[CH:8][CH:7]=1)=[O:5])[CH3:2].[OH:19][C@@H:20]([CH2:33][NH2:34])[CH2:21][O:22][C:23]1[C:31]2[NH:30][C:29](=[O:32])[NH:28][C:27]=2[CH:26]=[CH:25][CH:24]=1.C(O)(=O)C>C(O)C.[Pd]>[CH2:1]([O:3][C:4](=[O:5])[C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][CH:15]([NH:34][CH2:33][C@H:20]([OH:19])[CH2:21][O:22][C:23]3[C:31]4[NH:30][C:29](=[O:32])[NH:28][C:27]=4[CH:26]=[CH:25][CH:24]=3)[CH2:14][CH2:13]2)=[CH:8][CH:7]=1)[CH3:2]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 107991054-((2S)-3-Amino-2-hydroxy-propoxy)-1,3-dihydrobenzoimidazol-2-oneHCID 12717442Ethyl 4-(4-oxopiperidin-1-yl)benzoate

Product 1

HCID 102044924-[4-[(2S)-2-Hydroxy-3-(2-oxo-2,3-dihydro-1H-benzoimidazole-4-yloxy)-propylamino]-piperidin--1-yl}-benzoic acid ethyl esterYield 48.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A mixture of 1-(4-ethoxycarbonylphenyl)-4-piperidone (0.25 g, 1 mmol) (Taylor, E. C., Skotnicki, J. S. Synthesis, 1981, 606) and (S)-4-[2-hydroxy-3-aminopropoxy]-1,3-dihydro-2H-benzimidazol-2-one (0.22g, 1 mmol) (U.S. Pat. No. 5,786,356/1998) in 100 mL of ethanol and 0.5 mL of acetic acid was hydrogenated in the presence of 400 mg of 10% palladium on carbon under hydrogen (5˜20 psi) for overnight. The catalyst was then removed by filtering through a short pad of silica gel. The filtrate was concentrated and purified by thin layer chromatography (12% methanol/methylene chloride) to give the title compound as a white solid (0.22 g, 48%); mp >170° C. (decomposed); 1H NMR (300 MHz, DMSO-d6) δ 1.28 (t, J=7.0 Hz, 3H), 1.30-1.55 (m, 2H), 1.80-2.10 (m, 2H), 2.80-3.10 (m, 5H), 3.80-4.10 (m, 5H), 4.23 (q, J=7.0 Hz, 2H), 6.58 (d, J=7.8 Hz, 1H), 6.62 (d, J=8.4 Hz, 1H), 6.86 (dd, J=8.4, 7.8 Hz, 1H), 6.98 (d, J=8.6 Hz, 2H), 7.77 (d, J=8.6 Hz, 2H), 10.60 (s, 1H), 10.75 (s, 1H); MS (ES) m/z: 455.1 (MH+); HRMS Calcd. for C24H30N4O5 (MH+): 454.2216. Found: 454.2211.

Workup

  1. customThe catalyst was then removed
  2. filtrationby filtering through a short pad of silica gel
  3. concentrationThe filtrate was concentrated
  4. custompurified by thin layer chromatography (12% methanol/methylene chloride)

Sources & evidence

ORD record
ord-9dacfc00986247cebff765a310871b38
Source dataset
uspto-grants-2003_02
Patent number
US06525202B2

Reaction notes

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