Acetic Acid → 1-{5-[4-(2-Isopropoxy-phenyl)-piperazin-1-ylmethyl]-1-methyl-1H-pyrrol-2-ylmethyl}-piperidin-2-one

HRID 981512Notes

Reaction equation

HRID 981512 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)[CH3:3].[C:17](O)(=O)C.C=O.[CH3:23][N:24]1[CH:28]=[CH:27][CH:26]=[C:25]1[CH2:29][N:30]1[CH2:35][CH2:34][CH2:33][CH2:32][C:31]1=[O:36].[OH-].[Na+]>C(Cl)Cl.CO>[CH3:23][N:24]1[C:28]([CH2:17][N:14]2[CH2:13][CH2:12][N:11]([C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[O:4][CH:2]([CH3:1])[CH3:3])[CH2:16][CH2:15]2)=[CH:27][CH:26]=[C:25]1[CH2:29][N:30]1[CH2:35][CH2:34][CH2:33][CH2:32][C:31]1=[O:36]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 109440161-[2-(Propan-2-yloxy)phenyl]piperazineHCID 110087721-(1-Methylpyrrol-2-ylmethyl)-2-piperidinone

Product 1

HCID 99102571-{5-[4-(2-Isopropoxy-phenyl)-piperazin-1-ylmethyl]-1-methyl-1H-pyrrol-2-ylmethyl}-piperidin-2-oneYield 99.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 1-[2-(1-methylethoxy)phenyl]piperazine (9.38 g, 0.043 mole) as described in U.S. Pat. Nos. 4,547,505 and 4,438,115, glacial acetic acid (2.57 mL, 0.043 mole), and methanol (27 mL) was cooled in an ice bath and treated with 37% formalin (3.18 mL, 0.043 mole). A solution of 1-(1-methylpyrrol-2-ylmethyl)-2-piperidinone (8.19 g, 0.043 mole) and methanol (27 mL) was added and the resulting solution was stirred overnight at 25° C. under a dry nitrogen atmosphere. Methylene chloride (350 mL) was added followed by 3N sodium hydroxide solution (60 mL). After thorough mixing, the organic layer was separated, dried over anhydrous potassium carbonate, filtered and evaporated to give 18.20 g of 1-[[1-methyl-5-[[4-[2-(1-methylethoxy)phenyl]-1 -piperazinyl]methyl]-lH-pyrrol-2-yl]methyl]-2- piperidinone as a Yellow oil. This material (2.50 g) was dissolved in 6 mL ethanol and treated with 0.68 g of oxalic acid. The mixture was heated to effect solution, cooled and ether added until just cloudy. After cooling in an ice bath, a white solid was obtained by filtration. This was recrystallized twice from ethanol-ether using activated charcoal to give the oxalate salt, mp 139.5-140.5° C. (Ho).

Workup

  1. customAfter thorough mixing, the organic layer was separated
  2. dry with materialdried over anhydrous potassium carbonate
  3. filtrationfiltered
  4. customevaporated

Sources & evidence

ORD record
ord-e2fbb0a0fc324568ba5d801db724d9da
Source dataset
uspto-grants-1991_02
Patent number
US04992441

Reaction notes

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