4-Chlorobutyryl chloride → 1-(6-Acetyl-4-chloro-3'-fluoro-3-methylbiphenyl-2-yl)pyrrolidin-2-one

HRID 510834Notes

Reaction equation

HRID 510834 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)=[C:6]([C:15](=[O:17])[CH3:16])[CH:5]=[C:4]([Cl:18])[C:3]=1[CH3:19].Cl[CH2:21][CH2:22][CH2:23][C:24](Cl)=[O:25].CC(C)([O-])C.[K+]>CN(C)C1C=CN=CC=1.O1CCCC1>[C:15]([C:6]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)=[C:2]([N:1]2[CH2:21][CH2:22][CH2:23][C:24]2=[O:25])[C:3]([CH3:19])=[C:4]([Cl:18])[CH:5]=1)(=[O:17])[CH3:16]

Participants

6

Reactant 3

HCID 783704-Chlorobutyryl chlorideHCID 23665647Potassium tert-butoxideHCID 583684301-(6-Amino-4-chloro-3'-fluoro-5-methylbiphenyl-2-yl)ethanone

Product 1

HCID 866667671-(6-Acetyl-4-chloro-3'-fluoro-3-methylbiphenyl-2-yl)pyrrolidin-2-oneYield 30%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 1-(6-amino-4-chloro-3′-fluoro-5-methylbiphenyl-2-yl)ethanone (100 mg, 0.4 mmol) and 4-dimethylaminopyridine (52.8 mg, 0.432 mmol) in tetrahydrofuran (1 mL) was added 4-chlorobutanoyl chloride (0.044 mL, 0.40 mmol). The reaction was stirred at room temperature for 1 hour. Potassium tert-butoxide (1.0 M) in tetrahydrofuran (0.79 mL, 0.79 mmol) was added and the resulting mixture was stirred at room temperature for 2 hours, then quenched with aq. ammonium chloride and extracted with ethyl acetate. The combined organic layers were washed with water, brine, dried and evaporated. The resulting residue was purified on silica gel, eluting with 0 to 50% ethyl acetate in hexane, to give the product (40 mg, 30%). LCMS calculated for C19H18ClFNO2 (M+H)+: m/z=346.1. found: 346.1.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 2 hours
  2. customquenched with aq. ammonium chloride
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layers were washed with water, brine
  5. customdried
  6. customevaporated
  7. customThe resulting residue was purified on silica gel
  8. washeluting with 0 to 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-e8fdab7e8e4d4477ab95268edd4ecead
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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