Aluminum(III) Chloride → HCID 57743043, compound

HRID 1896483Notes

Reaction equation

HRID 1896483 reaction equation
Cl[CH2:2][N:3]1[CH2:7][CH:6]([CH:8]=[C:9]([F:11])[F:10])[CH2:5][C:4]1=[O:12].[Al+3].[Cl-].[Cl-].[Cl-].[Cl:17][C:18]1[CH:23]=[CH:22][N:21]2[N:24]=[C:25]([CH:27]3[CH2:29][CH2:28]3)[CH:26]=[C:20]2[N:19]=1>O1CCOCC1>[Cl:17][C:18]1[CH:23]=[CH:22][N:21]2[N:24]=[C:25]([CH:27]3[CH2:29][CH2:28]3)[C:26]([CH2:2][N:3]3[CH2:7][CH:6]([CH:8]=[C:9]([F:11])[F:10])[CH2:5][C:4]3=[O:12])=[C:20]2[N:19]=1

Participants

5

Reactant 3

HCID 6451240Aluminum(III) ChlorideHCID 53629214HCID 53629214, compoundHCID 53629215HCID 53629215, compound

Product 1

HCID 57743043HCID 57743043, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 1-(chloromethyl)-4-(2,2-difluorovinyl)pyrrolidin-2-one x276 (2.55 mmol, 2 eq, 500 mg) in 15 ml of dioxane at 0° C. are added successively AlCl3 (5.1 mmol, 2 eq, 680 mg) and 5-chloro-2-cyclopropylpyrazolo[1,5-a]pyrimidine x274 (2.55 mmol, 1 eq, 495 mg). The mixture is stirred at reflux for 1 hour, then quenched with an aqueous saturated NH4Cl solution and the resulting mixture extracted with AcOEt. The cumulated organic layers are washed with water, dried over MgSO4, filtered and evaporated under reduced pressure. The crude product is purified by chromatography on silicagel (CH2Cl2/MeOH/NH4OH: 98/2/0.2), followed by a crystallization step in hexane. 1-[(5-chloro-2-cyclopropyl pyrazolo[1,5-a]pyrimidin-3-yl)methyl]-4-(2,2-difluorovinyl)pyrrolidin-2-one 219 is obtained as a solid (623 mg).

Workup

  1. temperatureat reflux for 1 hour
  2. customquenched with an aqueous saturated NH4Cl solution
  3. extractionthe resulting mixture extracted with AcOEt
  4. washThe cumulated organic layers are washed with water
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe crude product is purified by chromatography on silicagel (CH2Cl2/MeOH/NH4OH: 98/2/0.2)
  9. customfollowed by a crystallization step in hexane

Sources & evidence

ORD record
ord-83d16f21bc3449708b51bc1fb7f59cc6
Source dataset
uspto-grants-2013_08
Patent number
US08518943B2

Reaction notes

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