Water → Prasugrel

HRID 1428164Notes

Reaction equation

HRID 1428164 reaction equation
[Si]([O:8][C:9]1[S:17][C:16]2[CH2:15][CH2:14][N:13]([CH:18]([C:26]([CH:28]3[CH2:30][CH2:29]3)=[O:27])[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[F:25])[CH2:12][C:11]=2[CH:10]=1)(C(C)(C)C)(C)C.C(N(CC)CC)C.[C:38](OC(=O)C)(=[O:40])[CH3:39].O>CC(C)=O.CN(C)C1C=CN=CC=1>[CH3:39][C:38]([O:8][C:9]1[S:17][C:16]2[CH2:15][CH2:14][N:13]([CH:18]([C:26]([CH:28]3[CH2:30][CH2:29]3)=[O:27])[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[F:25])[CH2:12][C:11]=2[CH:10]=1)=[O:40]

Participants

7

Reactant 4

HCID 962WaterHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 58516939HCID 58516939, compound

Product 1

HCID 6918456PrasugrelYield 85%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 180AcetoneSolvent2×

Conditions

Temperature
0 °C

Procedure

2-(Tert-butyldimethylsilyloxy)-5-(α-cyclopropylformyl-2-fluorobenzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine (3.0 g) prepared by example 2 was dissolved in acetone (10.0 mL) and the solution was cooled to 0° C. Triethylamine (1.02 g) was then added dropwise followed by adding 4-dimethylaminopyridine (DMAP) (0.025 g) and the mixture was stirred for 10 minutes at the same temperature. Acetic anhydride (0.83 g) in acetone was then added and the reaction was monitored by Thin Layer Chromatography (TLC) (petroleum ether/ethyl acetate=10/1 or 5/1). After the reaction was completed, cold water (7.5 mL) was then added to the reaction mixture. After the reaction mixture was stirred for 15 minutes, the reaction mixture was cooled to −5° C. and further stirred for 3 hours. Solid precipitate was collected by filtration followed by washing with a mixture of pre-cooled acetone/water (1:1 v/v) (10 ml). The obtained prasugrel free base was dried under vacuum at 50° C. for 24 hours. The yield was 85%.

Workup

  1. stirringAfter the reaction mixture was stirred for 15 minutes
  2. temperaturethe reaction mixture was cooled to −5° C.
  3. stirringfurther stirred for 3 hours
  4. filtrationSolid precipitate was collected by filtration
  5. washby washing with a mixture of pre-cooled acetone/water (1:1 v/v) (10 ml)
  6. dry with materialThe obtained prasugrel free base was dried under vacuum at 50° C. for 24 hours

Sources & evidence

ORD record
ord-78afbfcbf19342dfb024fa0da190575b
Source dataset
uspto-grants-2015_01
Patent number
US08937053B2

Reaction notes

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