Formaldehyde → 5-Chloro-1-(4-fluorophenyl)-3-[1-[2-(3-hydroxymethyl-2-imidazolidinon-1-yl)ethyl]-4-piperidyl]-1H-indole

HRID 22241Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[CH:6]=[C:5]2[CH:18]1[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][N:26]2[CH2:30][CH2:29][NH:28][C:27]2=[O:31])[CH2:20][CH2:19]1.[CH2:32]=[O:33]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=1)[CH:6]=[C:5]2[CH:18]1[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][N:26]2[CH2:30][CH2:29][N:28]([CH2:32][OH:33])[C:27]2=[O:31])[CH2:20][CH2:19]1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 5-chloro-1-(4-fluorophenyl)-3-[1-[2-(2-imidazolidinon-1-yl)ethyl]-4-piperidyl]-1H-indole (4.4 g) in tetrahydrofuran (25 ml) at room temperature was added dropwise a 30% aqueous solution of formaldehyde (800 mg). The mixture was heated at 50 ° C. for 2 h. Solvents were evaporated in vacuo and excess H2O was removed by evaporation with toluene. By addition of acetone the title compound crystallized. Recrystallization from acetone afforded 3.2 g of pure 5a. Mp: 118°-119 ° C. 1H NMR: δ1.85 (2H, dq), 2.05 (2H, broad d), 2.20 (2H, t), 2.60 (2H, t), 2.85 (1H, tt), 3.10 (2H, broad d), 3.40 (2H, t), 3.50 (4H), 4.80 (2H, s), 7.0-7.7 (8H).

Workup

customSolvents were evaporated in vacuo and excess H2O
customwas removed by evaporation with toluene
additionBy addition of acetone the title compound
customcrystallized
customRecrystallization from acetone

Sources & evidence

ORD record: ord-c11a2b95197042dea912efd71c8e7314
Source dataset: uspto-grants-1995_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05428036

Reaction notes

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