Tetrahydrofuran → 2-(4'-(Bis(4-chlorophenyl)amino)-[1,1'-biphenyl]-4-yl)-2-methylpropanenitrile

HRID 1488315Notes

Reaction equation

HRID 1488315 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)[C:9]2[CH:14]=[CH:13][C:12](B(O)O)=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.I[C:26]1[CH:31]=[CH:30][C:29]([C:32]([CH3:36])([CH3:35])[C:33]#[N:34])=[CH:28][CH:27]=1.O1CCCC1.C(=O)([O-])[O-].[Na+].[Na+]>O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)[C:9]2[CH:14]=[CH:13][C:12]([C:26]3[CH:31]=[CH:30][C:29]([C:32]([CH3:36])([CH3:35])[C:33]#[N:34])=[CH:28][CH:27]=3)=[CH:11][CH:10]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 10340Sodium CarbonateHCID 665799502-(4-Iodophenyl)-2-methylpropanenitrileHCID 71061297(4-(Bis(4-chlorophenyl)amino)phenyl)boronic acid

Product 1

HCID 710616702-(4'-(Bis(4-chlorophenyl)amino)-[1,1'-biphenyl]-4-yl)-2-methylpropanenitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

A 2 L flat bottomed flask fitted with an argon inlet and condenser was charged with (4-(bis(4-chlorophenyl)amino)phenyl)boronic acid (39.3 g), 2-(4-iodophenyl)-2-methylpropanenitrile, compound from Example 5 (c) (27.1 g) and tetrahydrofuran (591 mL). Sodium carbonate (33.9 g) was dissolved in water (393 mL) and this was added to the tetrahydrofuran mixture. The reaction mixture was then heated to 75° C. for 16 hours. Ethyl acetate (200 mL) and water (200 mL) were added and the mixture filtered through a celite pad. The layers were split, the organic layers washed with brine (600 mL), dried over MgSO4 and concentrated. The resulting material was purified by flash column chromatography eluting with ethyl acetate/heptane mixtures. The fractions were concentrated to a thick slurry and the solid filtered off, washed with heptane and dried under vacuum to give an off-white solid. Yield: 27 g. 1H NMR (400 MHz, CDCl3): δ 7.56-7.42 (6H, m, Ar—H), 7.21 (4H, m, Ar—H), 7.15-7.02 (6H, m, Ar—H), 1.77 (6H, s, CH3).

Workup

  1. customA 2 L flat bottomed flask fitted with an argon inlet and condenser
  2. filtrationthe mixture filtered through a celite pad
  3. customThe layers were split
  4. washthe organic layers washed with brine (600 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe resulting material was purified by flash column chromatography
  8. washeluting with ethyl acetate/heptane mixtures
  9. concentrationThe fractions were concentrated to a thick slurry
  10. filtrationthe solid filtered off
  11. washwashed with heptane
  12. customdried under vacuum
  13. customto give an off-white solid

Sources & evidence

ORD record
ord-599b4c49f3ec4261b09ad81f7d7311a4
Source dataset
uspto-grants-2016_08
Patent number
US09431145B2

Reaction notes

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