Phosphoric Acid → Sitagliptin Phosphate Monohydrate

HRID 870323Notes

Reaction equation

HRID 870323 reaction equation
[NH2:1][C@H:2]([CH2:19][C:20]1[CH:25]=[C:24]([F:26])[C:23]([F:27])=[CH:22][C:21]=1[F:28])[CH2:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]2[C:12]([C:15]([F:18])([F:17])[F:16])=[N:13][N:14]=[C:8]2[CH2:7]1)=[O:5].C([OH:32])(C)C.[P:33](=[O:37])([OH:36])([OH:35])[OH:34]>O>[CH2:11]1[N:6]([C:4]([CH2:3][C@H:2]([NH2:1])[CH2:19][C:20]2[C:21]([F:28])=[CH:22][C:23]([F:27])=[C:24]([F:26])[CH:25]=2)=[O:5])[CH2:7][C:8]2=[N:14][N:13]=[C:12]([C:15]([F:16])([F:18])[F:17])[N:9]2[CH2:10]1.[OH2:32].[OH:35][P:33]([OH:37])([OH:36])=[O:34]

Participants

5

Reactant 3

HCID 1004Phosphoric AcidHCID 3776IsopropanolHCID 4369359Sitagliptin2×

Product 1

HCID 11591741Sitagliptin Phosphate MonohydrateYield 68%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

7-[(3R)-3-Amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazine of Formula II (0.4 g), isopropanol (5 mL), water (0.4 mL), and phosphoric acid (0.11 g) are charged and heated to about 70° C. for about 3 hours. The reaction mass is then cooled to about 30° C. and stirred for about 10 hours. The separated solid is filtered and dried at about 45° C. under vacuum for about 4 hours to afford the title compound. (Yield: 68%; purity by HPLC: 96.67%; purity by chiral HPLC: 99.19%; m/z: 408(m+1); SOR: −21° C. (c=1% in water))

Workup

  1. temperatureThe reaction mass is then cooled to about 30° C.
  2. filtrationThe separated solid is filtered
  3. customdried at about 45° C. under vacuum for about 4 hours

Sources & evidence

ORD record
ord-b99d004bc0c14ef1b392587f20674ec2
Source dataset
uspto-grants-2015_03
Patent number
US08969558B2

Reaction notes

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