Phosphoric Acid → Sitagliptin Phosphate Monohydrate

HRID 870322Notes

Reaction equation

HRID 870322 reaction equation
[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].[P:29](=[O:33])([OH:32])([OH:31])[OH:30]>C(O)(C)C.O>[CH2:16]1[N:15]([C:13]([CH2:12][C@H:11]([NH2:28])[CH2:10][C:2]2[C:3]([F:9])=[CH:4][C:5]([F:8])=[C:6]([F:7])[CH:1]=2)=[O:14])[CH2:27][C:19]2=[N:20][N:21]=[C:22]([C:23]([F:24])([F:26])[F:25])[N:18]2[CH2:17]1.[OH2:30].[OH:31][P:29]([OH:33])([OH:32])=[O:30]

Participants

5

Reactant 2

HCID 1004Phosphoric AcidHCID 4369359Sitagliptin

Product 1

HCID 11591741Sitagliptin Phosphate MonohydrateYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
70 °C

Procedure

The sitagliptin freebase is dissolved in a mixture of isopropyl alcohol (5 mL) and water (0.2 mL), to which 85% phosphoric acid (0.056 g) is added. The contents are heated to about 70° C. for about 30 minutes, then cooled to about 30° C., and stirred for about 15 hours. The separated solid is filtered, washed with isopropyl alcohol (1 mL), and dried at about 50° C. for about 3 hours to afford the title compound. (Yield: 68%; purity by HPLC: 99.87%; SOR: −20.7° C. (c=1% in water))

Workup

  1. additionis added
  2. temperaturecooled to about 30° C.
  3. filtrationThe separated solid is filtered
  4. washwashed with isopropyl alcohol (1 mL)
  5. customdried at about 50° C. for about 3 hours

Sources & evidence

ORD record
ord-c4482f953ec4496198517ee7ecb97e8d
Source dataset
uspto-grants-2015_03
Patent number
US08969558B2

Reaction notes

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