Hydrochloric Acid → 1-[6-Chloro-2-(trifluoromethyl)-4-piperidinylmethyl]-2-pyrrolidinone

HRID 1088917Notes

Reaction equation

HRID 1088917 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH2:7][N:8]2[CH2:12][CH2:11][CH2:10][C:9]2=[O:13])=[CH:3][CH:2]=1.[ClH:14].[H][H].[OH-].[Na+].ClC1C=C(Cl)N=C([C:27]([F:30])([F:29])[F:28])N=1>O.C(#N)C>[Cl:14][CH:6]1[NH:1][CH:2]([C:27]([F:30])([F:29])[F:28])[CH2:3][CH:4]([CH2:7][N:8]2[CH2:12][CH2:11][CH2:10][C:9]2=[O:13])[CH2:5]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 117451541-(Pyridin-4-ylmethyl)pyrrolidin-2-one3×HCID 157131974,6-Dichloro-2-trifluoromethylpyrimidineHCID 178418361HCID 178418361, compound2×

Product 1

HCID 867442881-[6-Chloro-2-(trifluoromethyl)-4-piperidinylmethyl]-2-pyrrolidinone

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

To a solution of 1-(4-pyridinylmethyl)-2-pyrrolidinone (Intermediate compound IV, 905 g, 5.14 moles) in potable water (11 L) was added reagent grade hydrochloric acid (470 mL, about 5.65 moles) and platinum IV oxide (25 g). The stirred mixture was treated with hydrogen at low pressure (5 inches of water pressure) and after hydrogen uptake was complete (about 3 days) the catalyst was removed by filtration and sodium hydroxide (50% solution, 130 g, 14.1 moles) was added. Next acetonitrile (1.68 L) was added and the solution was cooled to 25° while rapidly stirring and 5.14 moles of 4,6-dichloro-2-trifluoromethylpyrimidine, V, was added dropwise over a period of about 2 hours. The temperature is generally held at or below 25° during this addition. The product separates during this addition or on continued stirring overnight and can be removed by filtration.

Workup

  1. custom(about 3 days)
  2. additionwas added
  3. temperaturethe solution was cooled to 25°
  4. custombelow 25°
  5. additionduring this addition
  6. additionThe product separates during this addition
  7. stirringon continued stirring overnight
  8. customcan be removed by filtration

Sources & evidence

ORD record
ord-e26813759eff4375b80ffe1e9039776a
Source dataset
uspto-grants-1990_10
Patent number
US04963678

Reaction notes

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