Hexane → Clopidogrel

HRID 270661

Reaction equation

HRID 270661 reaction equation
Br[CH2:2][CH2:3][C:4]1[S:5][CH:6]=[CH:7][C:8]=1[CH2:9]Br.Cl.[CH3:12][O:13][C:14](=[O:24])[C@H:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[Cl:23])[NH2:16].C(N(C(C)C)CC)(C)C.CCCCCC>C(#N)C.C(OCC)(=O)C>[Cl:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[C@H:15]([N:16]1[CH2:2][CH2:3][C:4]2[S:5][CH:6]=[CH:7][C:8]=2[CH2:9]1)[C:14]([O:13][CH3:12])=[O:24]

Participants

7

Reactant 4

HCID 8058HexaneHCID 81531DiisopropylethylamineHCID 24887640Benzeneacetic acid, alpha-amino-2-chloro-, methyl ester, hydrochloride (1:1), (alphaS)-HCID 693117222-(2-Bromoethyl)-3-(bromomethyl)thiophene

Product 1

HCID 60606ClopidogrelYield 88.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

5.0 g of 2-(2-bromoethyl)-3-bromomethylthiophene obtained in Example 7 was dissolved in 50 mL of acetonitrile, and added thereto was a solution obtained by dissolving 4.6 g of (S)-(+)-2-(2-chlorophenyl)glycine methyl ester hydrochloride and 6.8 g of diisopropylethylamine in 20 mL of acetonitrile over 30 minutes. The resulting mixture was refluxed for 8 hours, and concentrated by evaporation under reduced pressure. The residue was dissolved in 100 mL of ethyl acetate, and washed twice with 70 mL portions of water. The organic layer was washed with 50 mL of saturated sodium chloride aqueous solution and condensed under reduced pressure. The dark yellow colored oily residue thus obtained was subjected to a silica gel column chromatography (eluent, n-hexane:ethyl acetate=5:1) to obtain 5.0 g (yield of 88%) of the title compound as a yellowish oil.

Workup

  1. additionadded
  2. customobtained
  3. temperatureThe resulting mixture was refluxed for 8 hours
  4. concentrationconcentrated by evaporation under reduced pressure
  5. dissolutionThe residue was dissolved in 100 mL of ethyl acetate
  6. washwashed twice with 70 mL portions of water
  7. washThe organic layer was washed with 50 mL of saturated sodium chloride aqueous solution and condensed under reduced pressure
  8. customThe dark yellow colored oily residue thus obtained

Sources & evidence

ORD record
ord-ff48a41e3c0743829f51d117cdf112a8
Source dataset
uspto-grants-2008_11
Patent number
US07449580B2

Linked notes

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