4-Isopropoxyaniline → HCID 66604819, compound

HRID 2410695Notes

Reaction equation

HRID 2410695 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12](F)=[C:11]([C:16]#[N:17])[CH:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH:18]([O:21][C:22]1[CH:28]=[CH:27][C:25]([NH2:26])=[CH:24][CH:23]=1)([CH3:20])[CH3:19].CC([O-])(C)C.[K+]>CS(C)=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([NH:26][C:25]3[CH:24]=[CH:23][C:22]([O:21][CH:18]([CH3:20])[CH3:19])=[CH:28][CH:27]=3)=[C:11]([C:16]#[N:17])[CH:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 3

HCID 821124-IsopropoxyanilineHCID 23665647Potassium tert-butoxideHCID 66599429HCID 66599429, compound

Product 1

HCID 66604819HCID 66604819, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3′,4′-dichloro-4-fluorobiphenyl-3-carbonitrile (173 mg, 0.650 mmol), 4-isopropoxyaniline (108 mg, 0.715 mmol), and KOtBu (154 mg, 1.375 mmol) in DMSO (4 mL) was stirred at rt for 1.5 h, The mixture was diluted with ethyl acetate, washed with H2O and brine, and then dried over Na2SO4. The solvent was removed and the product was purified by silica gel chromatography (eluting with hexane containing 0 to 8% ethyl acetate) followed by preparative HPLC (100×30 mm Luna C18 column, flow rate 42 ml permin, gradient elution starting with A:B=50:50 and ending with A:B=0:100 [A=10 mM NH4OAc in 5% aqueous acetonitrile; B=10 mM NH4OAc in 95% aqueous acetonitrile] over 20 min). This afforded 99 mg of 3′,4′-dichloro-4-(4-isopropoxyphenylamino)-biphenyl-3-carbonitrile which still contained some impurities according to the LC/MS but was used as such for next step. MS (ESI) m/z 397.1 (M+H).

Workup

  1. washwashed with H2O and brine
  2. dry with materialdried over Na2SO4
  3. customThe solvent was removed
  4. customthe product was purified by silica gel chromatography (eluting with hexane containing 0 to 8% ethyl acetate)
  5. wash100×30 mm Luna C18 column, flow rate 42 ml permin, gradient elution
  6. waitB=10 mM NH4OAc in 95% aqueous acetonitrile] over 20 min)

Sources & evidence

ORD record
ord-00a882e2fa7d4b98903311b7a82b9f1f
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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