L-Malic Acid → HCID 131729737, compound

HRID 1928532Notes

Reaction equation

HRID 1928532 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].[C:29]([OH:37])(=[O:36])[C@H:30]([CH2:32][C:33]([OH:35])=[O:34])[OH:31]>C(OCC)(=O)C.C(O)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].[C:29]([O-:37])(=[O:36])[C@H:30]([CH2:32][C:33]([O-:35])=[O:34])[OH:31]

Participants

4

Reactant 2

HCID 222656L-Malic Acid2×HCID 4369359Sitagliptin2×

Product 1

HCID 131729737HCID 131729737, compoundYield 92.5%

Reagents, catalysts & solvents 1

HCID 21584252Ethanol ethylacetateSolvent2×

Conditions

Temperature
60 °C

Procedure

A 250 mL round flask was charged with Sitagliptin free base (5 g, 12 mmol) and a mixture of ethyl acetate:ethanol (5:0.8 v/v, 25 mL) was added. The mixture was mechanically stirred and heated to 60° C. until complete dissolution. The solution was then cooled to room temperature. In parallel, L-malic acid (1.65 g, 12 mmol) was completely dissolved in a mixture of ethyl acetate:ethanol (5:0.8 v/v, 10 mL) at 60° C. and then cooled to room temperature. The solution of the L-malic acid was then added dropwise to the solution of Sitagliptin free base over a period of 10 minutes while stirring at room temperature with the rotation speed of 310 rpm. The obtained white gel-paste reaction mixture was stirred at room temperature for about 69 hours. The obtained massive white precipitate was isolated by vacuum filtration, washed with cold mixture of ethyl acetate:ethanol (5:0.8 v/v, 2×10 mL) and dried in a vacuum oven at 40° C. for 23 hours to give Sitagliptin L-malate (5.99 g, 92% w/w yield).

Workup

  1. additionwas added
  2. temperatureThe solution was then cooled to room temperature
  3. temperaturecooled to room temperature
  4. stirringwhile stirring at room temperature with the rotation speed of 310 rpm
  5. customThe obtained white gel-paste reaction mixture
  6. stirringwas stirred at room temperature for about 69 hours
  7. customThe obtained massive white precipitate was isolated by vacuum filtration
  8. washwashed with cold mixture of ethyl acetate:ethanol (5:0.8 v/v, 2×10 mL)
  9. customdried in a vacuum oven at 40° C. for 23 hours

Sources & evidence

ORD record
ord-b159bb0175754baab8cd28902cac7fac
Source dataset
uspto-grants-2012_05
Patent number
US08183373B2

Reaction notes

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