Sulfuric Acid → Triprolidine

HRID 1803091Notes

Reaction equation

HRID 1803091 reaction equation
OS(O)(=O)=O.[CH3:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)(O)[CH2:14][CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:9][CH:8]=1.[OH-].[Na+]>O>[CH3:6][C:7]1[CH:12]=[CH:11][C:10](/[C:13](/[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)=[CH:14]\[CH2:15][N:16]2[CH2:17][CH2:18][CH2:19][CH2:20]2)=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 11970576alpha-(2-(1-Pyrrolidinyl)ethyl)-alpha-(p-tolyl)pyridine-2-methanol

Product 1

HCID 5282443TriprolidineYield 152.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

60 ml of demineralized water is charged into a round-bottomed flask kept at 25° to 30° C. and then slowly 540 ml of 90% Conc. H2SO4 is added and the temperature is raised to 40° C.-60° C. under stirring. Slowly 200 g of 1-(4-methylphenyl)-1-(2-pyridyl)-3-pyrrolidinopropan-1-ol is charged and the temperature is maintained at 85° C. under stirring. The reaction mass is heated to 100-105° C. and the temperature is maintained for 4 hours under stirring. After completion of the reaction, the reaction mass is cooled to 25°-30° C. and then poured into ice cold water (4 litre) at 5-10° C. under stirring over a period of an hour. 50% NaOH solution (w/w) is added slowly to the reaction mixture by maintaining the temperature at 5° to 20° C. over a period of 2 hours and the contents are stirred for an hour at 25° to 30° C. The reaction mixture is filtered under suction to obtain 286 g of wet triprolidine base comprising >92% E-isomer along with <8% Z-isomer. 2 litres of demineralized water and 286 g of wet triprolidine base are charged into a round-bottom flask at 25° to 30° C. and the contents are stirred for 3 hours by maintaining the same temperature. The contents are filtered and dried under suction for 2 hours. The process is repeated thrice to obtain 1-(4-methylphenyl)-1-(2-pyridyl)-3-pyrrolidino prop-1-ene (150 g, 80%) consisting of >98% E isomer along with <2% Z-isomer.

Workup

  1. customkept at 25° to 30° C.
  2. temperaturethe temperature is raised to 40° C.-60° C.
  3. stirringunder stirring
  4. temperatureThe reaction mass is heated to 100-105° C.
  5. temperaturethe temperature is maintained for 4 hours
  6. stirringunder stirring
  7. customAfter completion of the reaction
  8. temperaturethe reaction mass is cooled to 25°-30° C.
  9. stirringunder stirring over a period of an hour
  10. temperatureby maintaining the temperature at 5° to 20° C. over a period of 2 hours
  11. stirringthe contents are stirred for an hour at 25° to 30° C
  12. filtrationThe reaction mixture is filtered under suction

Sources & evidence

ORD record
ord-e6252ed01ae4443bb5bfef54f9e7fb1e
Source dataset
uspto-grants-2013_01
Patent number
US08350045B2

Reaction notes

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