Ethyl Acetate → Sitagliptin

HRID 870324Notes

Reaction equation

HRID 870324 reaction equation
[OH-].[Na+].C(OCC)(=O)C.[CH:9]1[C:10]([CH2:18][C@@H:19]([NH2:36])[CH2:20][C:21]([N:23]2[CH2:35][C:27]3=[N:28][N:29]=[C:30]([C:31]([F:34])([F:33])[F:32])[N:26]3[CH2:25][CH2:24]2)=[O:22])=[C:11]([F:17])[CH:12]=[C:13]([F:16])[C:14]=1[F:15].C1(C)C=CC(C(C([O-])=O)(O)C(C2C=CC(C)=CC=2)(O)C([O-])=O)=CC=1>O>[CH:9]1[C:10]([CH2:18][C@@H:19]([NH2:36])[CH2:20][C:21]([N:23]2[CH2:35][C:27]3=[N:28][N:29]=[C:30]([C:31]([F:34])([F:33])[F:32])[N:26]3[CH2:25][CH2:24]2)=[O:22])=[C:11]([F:17])[CH:12]=[C:13]([F:16])[C:14]=1[F:15]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 131730058HCID 131730058, compound

Product 1

HCID 4369359SitagliptinYield 92.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

10% sodium hydroxide solution (15 mL) is added to a mixture of ethyl acetate (25 mL), water (20 mL), and sitagliptin di-p-tolyl-tartarate salt (8.0 g) under stirring at about 5° C. The mixture is stirred for about 30 minutes. The layers are separated and the aqueous layer is extracted with ethyl acetate (50 mL). The combined organic layer is distilled off completely to afford 4.1 g of sitagliptin freebase.

Workup

  1. stirringThe mixture is stirred for about 30 minutes
  2. customThe layers are separated
  3. extractionthe aqueous layer is extracted with ethyl acetate (50 mL)
  4. distillationThe combined organic layer is distilled off completely

Sources & evidence

ORD record
ord-167f16c2196b478cafd1dfda415fbc31
Source dataset
uspto-grants-2015_03
Patent number
US08969558B2

Reaction notes

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