Water → Sitagliptin

HRID 1928530Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1928530
[CH:1]1[C:2]([CH2:10][C@@H:11]([NH2:28])[CH2:12][C:13]([N:15]2[CH2:27][C:19]3=[N:20][N:21]=[C:22]([C:23]([F:26])([F:25])[F:24])[N:18]3[CH2:17][CH2:16]2)=[O:14])=[C:3]([F:9])[CH:4]=[C:5]([F:8])[C:6]=1[F:7].O.OP(O)(O)=O.O.[OH-].[K+]>CC(OC)(C)C>[CH:1]1[C:2]([CH2:10][C@@H:11]([NH2:28])[CH2:12][C:13]([N:15]2[CH2:27][C:19]3=[N:20][N:21]=[C:22]([C:23]([F:26])([F:25])[F:24])[N:18]3[CH2:17][CH2:16]2)=[O:14])=[C:3]([F:9])[CH:4]=[C:5]([F:8])[C:6]=1[F:7]

Komponenten

5

Edukt 3

HCID 962WaterHCID 14797Potassium HydroxideHCID 11591741Sitagliptin Phosphate Monohydrate

Produkt 1

HCID 4369359SitagliptinAusbeute 177 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 15413tert-Butyl methyl etherLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Sitagliptin phosphate (80 g) was mixed with water (720 ml) and MTBE (240 ml) and cooled to 0° C. The mixture was basified with 33% KOH solution to pH 11, and the mixture was then warmed to 20° C. The phases were separated and the aqueous phase was extracted with MTBE (120 ml×2). This procedure was performed on an additional Sitagliptin phosphate batch (80 g). The combined organic layers were stirred 18 hours at −15° C. A white slurry mixture was obtained. The product was isolated by vacuum filtration, washed with MTBE (500 ml) and dried in a vacuum oven at 40° C. for 3 days to obtain Sitagliptin base (110.19 g, 85% yield).

Aufarbeitung

  1. temperaturethe mixture was then warmed to 20° C
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with MTBE (120 ml×2)
  4. customA white slurry mixture was obtained
  5. customThe product was isolated by vacuum filtration
  6. washwashed with MTBE (500 ml)
  7. customdried in a vacuum oven at 40° C. for 3 days

Quellen und Nachweise

ORD-Eintrag
ord-8c91e362761341068086a66db308b187
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08183373B2

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