Water → Prasugrel

HRID 1428166Notes

Reaction equation

HRID 1428166 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 90%

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 (1.0 eq.) prepared by example 4 was dissolved in acetone (10.0 mL) and the mixture was cooled to 0° C. Triethylamine (1.1 eq.) was added slowly followed by adding 4-dimethylaminopyridine (DMAP) (0.025 g) and the mixture was stirred for 10 minutes. Acetic anhydride (1.5 eq.) in acetone was then added. 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 added to the reaction mixture and the mixture was stirred for 15 minutes. It was then cooled to −5° C. and further stirred for 3 hours. After filtration, solid precipitate was washed 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 90%.

Workup

  1. stirringthe mixture was stirred for 15 minutes
  2. temperatureIt was then cooled to −5° C.
  3. stirringfurther stirred for 3 hours
  4. filtrationAfter filtration, solid precipitate
  5. washwas washed 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-a7749db02de248ecb5c58fbef01f6e7b
Source dataset
uspto-grants-2015_01
Patent number
US08937053B2

Reaction notes

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