Ethyl Acetate → Prasugrel

HRID 1975693Notes

Reaction equation

HRID 1975693 reaction equation
N1C=CC=CC=1.[CH:7]1([C:10]([CH:12]([N:20]2[CH2:25][CH2:24][CH:23]3[S:26][C:27](=[O:29])[CH:28]=[C:22]3[CH2:21]2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[F:19])=[O:11])[CH2:9][CH2:8]1.[H-].[Na+].[C:32](OCC)(=[O:34])[CH3:33]>CN(C)C=O.C(OC(=O)C)(=O)C>[C:32]([O:29][C:27]1[S:26][C:23]2[CH2:24][CH2:25][N:20]([CH:12]([C:10]([CH:7]3[CH2:8][CH2:9]3)=[O:11])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[F:19])[CH2:21][C:22]=2[CH:28]=1)(=[O:34])[CH3:33]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 19098215HCID 19098215, compound

Product 1

HCID 6918456PrasugrelYield 65%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 7918Acetic AnhydrideSolvent

Procedure

2.6 g (7.8 mmole) of 5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydrothieno[3,2-c]pyridine pyridine (prepared as described in Example 20) were dissolved in a mixture of 10 ml of dimethylformamide and 5 ml of acetic anhydride, and then 0.35 g (8.6 mmole) of a 60% w/w dispersion of sodium hydride in mineral oil was added to the resulting solution, whilst ice-cooling; the mixture was then stirred for 20 minutes at the same temperature, after which it was stirred for a further 3 hours at room temperature. At the end of this time, 300 ml of ethyl acetate were added to the mixture, which was then washed four times, each time with 50 ml of a saturated aqueous solution of sodium chloride The organic layer was separated and dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The resulting residue was subjected to silica gel column chromatography, using a 100:3 by volume mixture of toluene and ethyl acetate as the eluent, to give a yellow oil. This oil was crystallized from diisopropyl ether, to obtain the title compound as white crystals, melting at 120°-121.5° C., in a yield of 65%.

Workup

  1. temperaturecooling
  2. stirringafter which it was stirred for a further 3 hours at room temperature
  3. washwas then washed four times
  4. customeach time with 50 ml of a saturated aqueous solution of sodium chloride The organic layer was separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was removed by evaporation under reduced pressure
  7. additionby volume mixture of toluene and ethyl acetate as the eluent
  8. customto give a yellow oil
  9. customThis oil was crystallized from diisopropyl ether

Sources & evidence

ORD record
ord-f6fac6878de5482daf050cded7109608
Source dataset
uspto-grants-1994_02
Patent number
US05288726

Reaction notes

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