Diisopropyl Ether → N-Boc-sitagliptin

HRID 590634

Reaktionsgleichung

Reaktionsgleichung von HRID 590634
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])[CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C(C[C@@H](N)CC([N:38]2[CH2:50][C:42]3=[N:43][N:44]=[C:45]([C:46]([F:49])([F:48])[F:47])[N:41]3[CH2:40][CH2:39]2)=O)=C(F)C=C(F)C=1F.O.OP(O)(O)=O.CCN(C(C)C)C(C)C.Cl.FC(F)(F)C1N2CCNCC2=NN=1.ClC1C=C(B(O)O)C=CC=1.C(OC(C)C)(C)C>O.C1(C)C(C)=CC=CC=1>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH2:10][C:11](=[O:13])[N:38]1[CH2:39][CH2:40][N:41]2[C:45]([C:46]([F:49])([F:47])[F:48])=[N:44][N:43]=[C:42]2[CH2:50]1)[CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])([CH3:2])([CH3:3])[CH3:4]

Komponenten

9

Edukt 6

HCID 7914Diisopropyl EtherHCID 81531DiisopropylethylamineHCID 2734323(3-Chlorophenyl)boronic acidHCID 11591741Sitagliptin phosphate monohydrateHCID 119613713-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochlorideHCID 21911205Boc-(R)-3-Amino-4-(2,4,5-trifluoro-phenyl)-butyric acid

Produkt 1

HCID 46836576N-Boc-sitagliptin

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 7237O-XyleneLösungsmittel

Versuchsvorschrift

5 g of 3-tert-butoxycarbonylamino-4-(2,4,5-trifluorophenyl)butyric acid of formula (II) was charged with 40 ml of xylene into a 500 ml 4 necked round bottom flask attached with dean stark apparatus followed by 5 ml of Hunig's base at room temperature. Then 5 g of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine HCl was charged and stirred for 5 minutes. 2.34 g of 3-chloro phenyl boronic acid was charged to the reaction mass. After 48 hours of stirring at reflux temperature, the reaction was complete. The reaction mass was cooled to room temperature and 50 ml of water was added to it. The organic layer was separated and washed twice with 25 ml of 1N HCl. The organic layer was separated and washed with 25 ml of water followed by 6% NaHCO3 and finally by 25 ml of water. The organic layer was then separated, treated with sodium sulfate and then with charcoal and filtered. The solvent was distilled out under vacuum. The solid obtained was stirred with 25 ml of diisopropyl ether for 2 hours, filtered, washed with diisopropyl ether and then dried under vacuum at 50° C. for 12-15 hours.

Aufarbeitung

  1. stirringAfter 48 hours of stirring
  2. temperatureat reflux temperature
  3. customThe organic layer was separated
  4. washwashed twice with 25 ml of 1N HCl
  5. customThe organic layer was separated
  6. washwashed with 25 ml of water
  7. customThe organic layer was then separated
  8. additiontreated with sodium sulfate
  9. filtrationwith charcoal and filtered
  10. distillationThe solvent was distilled out under vacuum
  11. customThe solid obtained
  12. filtrationfiltered
  13. washwashed with diisopropyl ether
  14. customdried under vacuum at 50° C. for 12-15 hours

Quellen und Nachweise

ORD-Eintrag
ord-fab43256c2d74117ab899db88cf0255c
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09233967B2

Verknüpfte Notizen

Wird geladen…