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Pyridine → 1-(6-Acetyl-4-chloro-3',5'-difluoro-3-methylbiphenyl-2-yl)pyrrolidin-2-one

HRID 510838
Notes
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Reaction equation

HRID 510838 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[CH:13]=[C:12]([F:14])[CH:11]=[C:10]([F:15])[CH:9]=2)=[C:6]([C:16](=[O:18])[CH3:17])[CH:5]=[C:4]([Cl:19])[C:3]=1[CH3:20].N1C=CC=CC=1.Cl[CH2:28][CH2:29][CH2:30][C:31](Cl)=[O:32].CC(C)([O-])C.[K+]>C(Cl)Cl.O1CCCC1>[C:16]([C:6]1[C:7]([C:8]2[CH:9]=[C:10]([F:15])[CH:11]=[C:12]([F:14])[CH:13]=2)=[C:2]([N:1]2[CH2:28][CH2:29][CH2:30][C:31]2=[O:32])[C:3]([CH3:20])=[C:4]([Cl:19])[CH:5]=1)(=[O:18])[CH3:17]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 1049PyridineHCID 783704-Chlorobutyryl chlorideHCID 23665647Potassium tert-butoxideHCID 583685171-(6-Amino-4-chloro-3',5'-difluoro-5-methylbiphenyl-2-yl)ethanone

Product 1

HCID 866667701-(6-Acetyl-4-chloro-3',5'-difluoro-3-methylbiphenyl-2-yl)pyrrolidin-2-oneYield 12.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 1-(6-amino-4-chloro-3′,5′-difluoro-5-methylbiphenyl-2-yl)ethanone (0.10 g, 0.34 mmol) and pyridine (0.041 mL, 0.51 mmol) in methylene chloride (2 mL) was added 4-chlorobutanoyl chloride (0.042 mL, 0.37 mmol). The reaction was stirred at room temperature for 1 hour, quenched with saturated sodium bicarbonate solution and extracted with ethyl acetate. The combined extracts were dried over MgSO4 and concentrated to dryness under reduced pressure. The resulting residue was treated with 1.0 M potassium tert-butoxide in tetrahydrofuran (0.84 mL, 0.84 mmol) in tetrahydrofuran (2 mL) at room temperature for 2 hours. The reaction was quenched with aq. NH4Cl, extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over MgSO4 and evaporated. The residue was purified on silica gel (eluting with 0-40% of ethyl acetate in hexanes) to give the desired product (15 mg, 12%), LCMS calculated for C19H17ClF2NO2 (M+H)+: m/z=364.1. found: 364.1.

Workup

  1. customquenched with saturated sodium bicarbonate solution
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined extracts were dried over MgSO4
  4. concentrationconcentrated to dryness under reduced pressure
  5. customThe reaction was quenched with aq. NH4Cl
  6. extractionextracted with ethyl acetate
  7. washThe combined organic layers were washed with water and brine
  8. dry with materialdried over MgSO4
  9. customevaporated
  10. customThe residue was purified on silica gel (eluting with 0-40% of ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-62fca9299ef04353baa6f7459e73d2f5
Source dataset
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09096600B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes