Sodium Bicarbonate → Risperidal iMpurity B

HRID 969733Notes

Reaction equation

HRID 969733 reaction equation
Cl[CH2:2][CH2:3][C:4]1[C:9](=[O:10])[N:8]2[CH2:11][CH2:12][CH2:13][CH2:14][C:7]2=[N:6][C:5]=1[CH3:15].Cl.[F:17][C:18]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:19]=1[C:20](=[N:27][OH:28])[CH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C(=O)([O-])O.[Na+]>C(#N)C.[I-].[K+]>[F:17][C:18]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:19]=1[C:20](=[N:27][OH:28])[CH:21]1[CH2:26][CH2:25][N:24]([CH2:2][CH2:3][C:4]2[C:9](=[O:10])[N:8]3[CH2:11][CH2:12][CH2:13][CH2:14][C:7]3=[N:6][C:5]=2[CH3:15])[CH2:23][CH2:22]1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 27630793-(2-Chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4hpyrido(1,2-a)pyrimidin-4-oneHCID 57357481Methanone, (2,4-difluorophenyl)-4-piperidinyl-, oxime, hydrochloride (1:1)

Product 1

HCID 71433889Risperidal iMpurity BYield 92.5%

Reagents, catalysts & solvents 2

HCID 4875Potassium IodideCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of 36.0 g (0.16 mole) of 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one in 800 ml of acetonitrile 44.3 g of 4-(2,4-difluoro-benzoyl)-piperidine-oxime-hydrochloride, 33.6 g of sodium hydrogen carbonate and 0.66 g (4 millimoles) of potassium iodide are added. The reaction mixture is refluxed for 5 hours, cooled to room temperature and the solvent is removed in vacuo. The residue is taken up in 700 ml of water and extracted twice with 600 ml of dichloromethane each. The combined organic layers are dried over sodium sulfate and evaporated in vacuo. Thus 63.7 g of the title compound are obtained. Yield 92.5%. M.p.: 180-183° C.

Workup

  1. temperatureThe reaction mixture is refluxed for 5 hours
  2. customthe solvent is removed in vacuo
  3. extractionextracted twice with 600 ml of dichloromethane each
  4. dry with materialThe combined organic layers are dried over sodium sulfate
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-d736e404b79343de9a0344cdbc43413e
Source dataset
uspto-grants-2007_12
Patent number
US07307168B2

Reaction notes

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