Hydrochloric Acid → 2-(Pyrrolidin-3-yl)pyridine

HRID 2178514Notes

Reaction equation

HRID 2178514 reaction equation
C([N:8]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:9]1)C1C=CC=CC=1.C([O-])=O.[NH4+].Cl>CO.O.C(O)(C)C.[Pd]>[NH:8]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:9]1

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 2723923Ammonium formateHCID 109556222-(1-Benzylpyrrolidin-3-yl)pyridine

Product 1

HCID 50139382-(Pyrrolidin-3-yl)pyridineYield 85%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 3776IsopropanolSolvent2×

Conditions

Temperature
68 °C

Procedure

To 2-(1-benzylpyrrolidin-3-yl)pyridine enantiomer 1 a1-64 (10.01 g, 41.96 mmol, 1 eq) in methanol (340 ml) is added Pd/C (5%, 1.98 g). A solution of ammonium formate (10.69 g, 167.83 mmol, 4 eq) in water (55 ml) is then added dropwise over a period of 10 minutes. The reaction mixture is heated for 45 mins at 68° C., then cooled to room temperature. The catalyst is filtered off using Celite, washed with methanol (60 ml) and the pooled filtrates evaporated to dryness. The residue is retaken in methanol (50 ml) and evaporated again. Dichloromethane (100 ml) is added to the residue, the solid obtained is filtered, washed with dichloromethane (30 ml) and the pooled filtrates are evaporated to dryness to give a yellow oil. This oil is dissolved in isopropanol (60 ml) and a mixture of isopropanol (21 ml)/aqueous HCl 6N (21 ml, 3 eq) is added slowly over a period of 15 minutes to the solution. The mixture is stirred at room temperature overnight, the precipitate obtained is filtered, washed with isopropanol (10 ml) and dried under vacuum for 4 hours at 40° C. to afford 7.90 g of 2-(pyrrolidin-3-yl)pyridine enantiomer 1 dihydrochloride a1-66. Yield: 85%.

Workup

  1. temperaturecooled to room temperature
  2. filtrationThe catalyst is filtered off
  3. washwashed with methanol (60 ml)
  4. customthe pooled filtrates evaporated to dryness
  5. customevaporated again
  6. additionDichloromethane (100 ml) is added to the residue
  7. customthe solid obtained
  8. filtrationis filtered
  9. washwashed with dichloromethane (30 ml)
  10. customthe pooled filtrates are evaporated to dryness
  11. customto give a yellow oil
  12. additionis added slowly over a period of 15 minutes to the solution
  13. customthe precipitate obtained
  14. filtrationis filtered
  15. washwashed with isopropanol (10 ml)
  16. customdried under vacuum for 4 hours at 40° C.

Sources & evidence

ORD record
ord-422737390166480d80ae67b430625ff7
Source dataset
uspto-grants-2015_06
Patent number
US09067930B2

Reaction notes

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