Acetonitrile → A-431404

HRID 1064716

Reaction equation

HRID 1064716 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[C:12](I)[CH:11]=2)=[O:9])=[CH:4][CH:3]=1.[CH2:18]([N:22]1[CH2:26][CH2:25][CH2:24][C@H:23]1[CH3:27])[CH2:19][C:20]#[CH:21].C(#N)C.CC1C=CC(P(C2C=CC(C)=CC=2)C2C=CC(C)=CC=2)=CC=1.C(NC(C)C)(C)C>CC([O-])=O.CC([O-])=O.[Pd+2].[Cu](I)I>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]3[O:16][C:20]([CH2:19][CH2:18][N:22]4[CH2:26][CH2:25][CH2:24][C@H:23]4[CH3:27])=[CH:21][C:12]=3[CH:11]=2)=[O:9])=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 6342AcetonitrileHCID 7912DiisopropylamineHCID 13956Phosphine, tris(4-methylphenyl)-HCID 11367023(R)-1-(But-3-yn-1-yl)-2-methylpyrrolidineHCID 11382275(4-Fluorophenyl)(4-hydroxy-3-iodophenyl)methanone

Product 1

HCID 9906447A-431404Yield 18%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
25 °C

Procedure

The product from Example 68A (6.5 g, 18.5 mmol) was sequentially treated with a 0.1M solution of the product from Example 68B in acetonitrile (230 mL, 23.0 mmol), Pd(OAc)2 (0.127 g, 0.566 mmol), tris(4-methylphenyl)phosphine (0.344 g, 1.130 mmol), and copper iodide (1.08 g, 95.72 mmol). After stirring at 25° C. for 10 minutes, the reaction mixture was treated with diisopropyl amine (26.6 mL, 189 mmol) and then heated at 60° C. in an inert atmosphere for 16 hours. The reaction mixture was allowed to cool to room temperature, filtered through celite, and the filtrate concentrated under reduced pressure. The residue was purified on silica gel using 90% DCM, 9.9% MeOH, 0.1% NH4OH to provide the title compound (1.21 g, 18.0% yield). 1HNMR (300 MHz, CD3OD) δ 1.09 (d, 3H, J=6.1 Hz), 1.46 (m, 1H), 1.81 (m, 2H), 2.02-2.28 (m, 2H), 2.49 (m, 2H) 3.06 (m, 2H), 3.28 (m, 2H), 6.68 (s, 1H),), 7.27 (t, 2H), 7.58 (d, 1H, J=8.9 Hz), 7.71 (d, 1H, J=8.9 Hz) 7.86 (t, 2H), 7.97 (s, 1H); MS (ESI) m/z 352 (M+H)+.

Workup

  1. temperatureheated at 60° C. in an inert atmosphere for 16 hours
  2. temperatureto cool to room temperature
  3. filtrationfiltered through celite
  4. concentrationthe filtrate concentrated under reduced pressure
  5. customThe residue was purified on silica gel using 90% DCM, 9.9% MeOH, 0.1% NH4OH

Sources & evidence

ORD record
ord-3a21f7820e58445fa6019df6a5e69c41
Source dataset
uspto-grants-2005_11
Patent number
US06969730B2

Linked notes

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