Ethyl nipecotate → (R)-(-)-Ethyl Nipecotate Tartrate

HRID 1058094Notes

Reaction equation

HRID 1058094 reaction equation
[C:1]([OH:10])(=[O:9])[C@@H:2]([C@H:4]([C:6]([OH:8])=[O:7])[OH:5])[OH:3].[NH:11]1[CH2:21][CH2:20][CH2:19][CH:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:12]1.N1CCC[C@@H](C(OCC)=O)C1.C([C@@H]([C@H](C([O-])=O)O)O)([O-])=O>C(O)(C)C.O>[C:6]([CH:4]([CH:2]([C:1]([OH:10])=[O:9])[OH:3])[OH:5])([OH:8])=[O:7].[NH:11]1[CH2:21][CH2:20][CH2:19][C@@H:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:12]1

Participants

6

Reactant 3

HCID 98969Ethyl nipecotateHCID 444305L-Tartaric acidHCID 86758823(R)-(-)-ethyl nipecotate L-(+)-tartrate

Product 1

HCID 2733695(R)-(-)-Ethyl Nipecotate TartrateYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
62.5 °C

Procedure

L-(+)-Tartaric acid (47.74 g, 318 mmol) was suspended in 265 g of isopropyl alcohol and 16.91 g of water. The mixture was heated to 60-65° C. to afford a homogeneous solution. One equivalent of (±)-ethyl nipecotate (50 g, 318 mmol) was added while the temperature was maintained at or below 75° C. The mixture was stirred at 70-75° C. for 20-30 minutes, then cooled to 60° C. over 60 minutes. Seed crystals of (R)-(−)-ethyl nipecotate-L-(+)-tartrate (25 mg, 0.08 mmol) were added and the reaction was cooled to 26-30° C. over three hours. The temperature was maintained at 26-30° C. for 30 minutes until precipitation was complete. The product was isolated (62.0 g, 94.8% de) and washed twice with a mixture of isopropyl alcohol (21.05 g) and water (1.34 g). The crude product was slurried in a mixture of isopropyl alcohol (188 g) and water (12 g) at 73-77° C. After stirring for 10-20 minutes, the suspension was cooled to 26-30° C. Temperatures exceeding 30° C. will result in less yield, while a temperature of less than 25° C. resulted in de<98%. The product was isolated by filtration and washed twice with a mixture of isopropyl alcohol (21.05 g) and water (1.34 g). This afforded the title compound as a white powder in 72% yield, 98.8% de.

Workup

  1. customto afford a homogeneous solution
  2. temperaturewas maintained at or below 75° C
  3. temperaturecooled to 60° C. over 60 minutes
  4. temperaturethe reaction was cooled to 26-30° C. over three hours
  5. temperatureThe temperature was maintained at 26-30° C. for 30 minutes until precipitation
  6. customThe product was isolated (62.0 g, 94.8% de)
  7. washwashed twice with a mixture of isopropyl alcohol (21.05 g) and water (1.34 g)
  8. additionThe crude product was slurried in a mixture of isopropyl alcohol (188 g) and water (12 g) at 73-77° C
  9. stirringAfter stirring for 10-20 minutes
  10. temperaturethe suspension was cooled to 26-30° C
  11. customexceeding 30° C.
  12. customwill result
  13. customin less yield, while a temperature of less than 25° C.
  14. customresulted in de<98%
  15. customThe product was isolated by filtration
  16. washwashed twice with a mixture of isopropyl alcohol (21.05 g) and water (1.34 g)

Sources & evidence

ORD record
ord-fe05e1da699444369549defde138d795
Source dataset
uspto-grants-2003_02
Patent number
US06515130B1

Reaction notes

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