Phosphoric Acid → 1-Methyl-4-(3-methoxyphenyl)-1,2,3,6-tetrahydropyridine

HRID 2106888Notes

Reaction equation

HRID 2106888 reaction equation
P(=O)(O)(O)O.[CH3:6][O:7][C:8]1[CH:9]=[C:10]([C:14]2(O)[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)[CH:11]=[CH:12][CH:13]=1.[OH-].[NH4+]>O>[CH3:6][O:7][C:8]1[CH:9]=[C:10]([C:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH:15]=2)[CH:11]=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 1004Phosphoric AcidHCID 14923Ammonium HydroxideHCID 13640221HCID 13640221, compound

Product 1

HCID 1557781-Methyl-4-(3-methoxyphenyl)-1,2,3,6-tetrahydropyridineYield 97.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To 4.075 liters of 85% phosphoric acid at 60° C. in a 22 liter flask equipped with a condenser, thermometer, and stirrer was added portionwise 1.015 kg (4.35 mol) of 4-(3-methoxyphenyl)-1-methyl-4-piperidinol via a powder funnel. The reaction mixture was stirred for 3 hours at a temperature between 70° C. and 80° C. whereupon 4 liters of water was added and the temperature of the reaction mixture adjusted to approximately 50° C. The mixture was neutralized to pH 8.5 by the addition of 8.5 liters of 28% ammonium hydroxide while maintaining the temperature of the reaction mixture above 50° C. The resulting aqueous solution was extracted at 60° C. with 1.25 liters of hexane three times. The organic extracts were combined and washed twice with 1 liter of water, once with 0.5 liters of saturated sodium chloride solution and dried over 250 g of anhydrous sodium sulfate. Evaporation of the volatiles under reduced pressure provided 862.5 g of 97.9% pure 1,2,3,6-tetrahydro-4-(3-methoxyphenyl)-1-methylpyridine. Yield 97.7%. mp (hydrobromide salt)=139.5°-141° C.

Workup

  1. additionwas added
  2. customadjusted to approximately 50° C
  3. temperaturewhile maintaining the temperature of the reaction mixture above 50° C
  4. extractionThe resulting aqueous solution was extracted at 60° C. with 1.25 liters of hexane three times
  5. washwashed twice with 1 liter of water, once with 0.5 liters of saturated sodium chloride solution
  6. dry with materialdried over 250 g of anhydrous sodium sulfate
  7. customEvaporation of the volatiles under reduced pressure

Sources & evidence

ORD record
ord-c60349ee52214434b4f724c9720360ca
Source dataset
uspto-grants-1990_06
Patent number
US04931558

Reaction notes

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