Formaldehyde → (S)-Methyl 1-methylpyrrolidine-2-carboxylate

HRID 21753

Reaktionsgleichung

Reaktionsgleichung von HRID 21753
S(=O)(=O)(O)O.[NH:6]1[CH2:13][CH2:12][CH2:11][C@H:7]1[C:8]([OH:10])=O.[C:14]([O-])([O-])=O.[K+].[K+].[CH2:20]=[O:21].[BH4-].[Na+]>O.CO>[CH3:20][O:21][C:8](=[O:10])[C@@H:7]1[CH2:11][CH2:12][CH2:13][N:6]1[CH3:14]

Komponenten

8

Edukt 5

HCID 712FormaldehydeHCID 1118Sulfuric AcidHCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 4311764Sodium borohydride

Produkt 1

HCID 10920622(S)-Methyl 1-methylpyrrolidine-2-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittel2×HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Methanol (2.2 L, 68.66 mol) was stirred under nitrogen and cooled to 0° C. Sulfuric acid (97%, 0.179 L, 3.26 mol) was added with vigorous stirring at a rate such that the internal temperature of the reactor did not rise above 10° C. L-Proline (0.5 kg, 4.34 mol) was added to the methanol, and the reaction was refluxed for 18 hr. The reaction mixture was cooled to 0° C., and with vigorous stirring a solution of K2CO3 (0.217 kg, 1.57 mol) in 0.363 L of water was slowly added to the mixture, until the pH was between pH 7 and 8. The neutralized solution was again cooled to 0° C., and aqueous formaldehyde solution (36%, 0.543 L) was added. After stirring for 15 min, 0.082 kg (2.17 mol) of powdered sodium borohydride was added in portions while maintaining the temperature between -5° and +5° C. The suspension was stirred for 3 hr, then filtered, and the filter cake was washed with toluene. The combined organic solvents were diluted 1:1 with water (2.6 L) and filtered. The organic phase was separated, and the aqueous layer was extracted at 0° C. with 5×0.5 L portions of toluene. The toluene extracts were combined, dried over sodium sulfate and filtered. The volume of the solution was reduced by half by distillation at 60° C. and 90 mbar pressure. The solution was taken to the next step without further purification.

Aufarbeitung

  1. customdid not rise above 10° C
  2. temperaturethe reaction was refluxed for 18 hr
  3. temperatureThe reaction mixture was cooled to 0° C.
  4. additionwas slowly added to the mixture, until the pH
  5. temperatureThe neutralized solution was again cooled to 0° C.
  6. stirringAfter stirring for 15 min
  7. temperaturewhile maintaining the temperature between -5° and +5° C
  8. stirringThe suspension was stirred for 3 hr
  9. filtrationfiltered
  10. washthe filter cake was washed with toluene
  11. additionThe combined organic solvents were diluted 1:1 with water (2.6 L)
  12. filtrationfiltered
  13. customThe organic phase was separated
  14. extractionthe aqueous layer was extracted at 0° C. with 5×0.5 L portions of toluene
  15. dry with materialdried over sodium sulfate
  16. filtrationfiltered
  17. distillationThe volume of the solution was reduced by half by distillation at 60° C.
  18. customThe solution was taken to the next step without further purification

Quellen und Nachweise

ORD-Eintrag
ord-545a2659e6fa4d5da251bc882e1a77a2
Quelldatensatz
uspto-grants-1995_06
Patentnummer
US05424444

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