Sodium Carbonate → 4-(5-{[3,3-Bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl]methyl}-1,2,4-oxadiazol-3-yl)benzonitrile

HRID 1667272Notes

Reaction equation

HRID 1667272 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[C:11]([CH2:13][N:14]3[CH2:18][CH2:17][C:16]([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)([C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)[C:15]3=[O:33])[O:10][N:9]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:40][N:41](C)C(=O)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.O.O.O.[K+].[K+].[K+].[K+].[Fe+2]>[F:25][C:22]1[CH:23]=[CH:24][C:19]([C:16]2([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[CH2:17][CH2:18][N:14]([CH2:13][C:11]3[O:10][N:9]=[C:8]([C:5]4[CH:6]=[CH:7][C:2]([C:40]#[N:41])=[CH:3][CH:4]=4)[N:12]=3)[C:15]2=[O:33])=[CH:20][CH:21]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 31374DimethylacetamideHCID 673770311-((3-(4-Bromophenyl)-1,2,4-oxadiazol-5-yl)methyl)-3,3-bis(4-fluorophenyl)pyrrolidin-2-one

Product 1

HCID 673776574-(5-{[3,3-Bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl]methyl}-1,2,4-oxadiazol-3-yl)benzonitrile

Reagents, catalysts & solvents 2

HCID 161067Potassium ferrocyanide trihydrateCatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
120 °C

Procedure

1-((3-(4-Bromophenyl)-1,2,4-oxadiazol-5-yl)methyl)-3,3-bis(4-fluorophenyl)pyrrolidin-2-one (233 mg, 0.457 mmol; Example 235A), palladium(II) acetate (1.025 mg, 4.57 μmol), sodium carbonate (48.4 mg, 0.457 mmol) and potassium hexacyanoferrate(II) trihydrate (42.4 mg, 0.100 mmol) in N,N-dimethylacetamide (2 mL) was placed under nitrogen and heated to 120° C. The reaction was cooled, loaded onto a GraceResolv™ 40 g silica gel column (Grace Davison Discovery Sciences) and the product eluted with a gradient of 5% ethyl acetate/hexanes to 40% ethyl acetate/hexanes (Flow=40 mL/minute) over 40 minutes to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.08 (d, J=8.4, 2H), 7.78 (d, J=8.4, 2H), 7.38-7.30 (m, 4H), 7.07-6.98 (m, 4H), 4.89 (s, 2H), 3.57 (t, J=6.5, 2H), 2.84 (t, J=6.4, 2H); MS (ESI−) m/z 455.1 (M−H)−.

Workup

  1. temperatureThe reaction was cooled
  2. washthe product eluted with a gradient of 5% ethyl acetate/hexanes to 40% ethyl acetate/hexanes (Flow=40 mL/minute) over 40 minutes

Sources & evidence

ORD record
ord-31574b1fb5924702acfdf720608f5d1a
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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