Acetic Acid → 4-(benzylthio)-N-(4'-chloro-2-fluoro-5-methoxy-3'-methyl-[1,1'-biphenyl]-4-yl)benzene-1,2-diamine

HRID 1504387Notes

Reaction equation

HRID 1504387 reaction equation
[CH2:1]([S:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:21]([O:22][CH3:23])=[CH:20][C:19]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([CH3:31])[CH:25]=3)=[C:18]([F:32])[CH:17]=2)=[C:11]([N+:33]([O-])=O)[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=O)C>[Zn]>[CH2:1]([S:8][C:9]1[CH:10]=[C:11]([NH2:33])[C:12]([NH:15][C:16]2[C:21]([O:22][CH3:23])=[CH:20][C:19]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([CH3:31])[CH:25]=3)=[C:18]([F:32])[CH:17]=2)=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 117737265N-(4-(benzylthio)-2-nitrophenyl)-4'-chloro-2-fluoro-5-methoxy-3'-methyl-[1,1'-biphenyl]-4-amine

Product 1

HCID 1177370484-(benzylthio)-N-(4'-chloro-2-fluoro-5-methoxy-3'-methyl-[1,1'-biphenyl]-4-yl)benzene-1,2-diamineYield 78%

Reagents, catalysts & solvents 1

HCID 23994ZincCatalyst

Conditions

Temperature
70 °C

Procedure

To a vial was added N-(4-(benzylthio)-2-nitrophenyl)-4′-chloro-2-fluoro-5-methoxy-3′-methyl-[1,1′-biphenyl]-4-amine (2.56 g, 5.03 mmol), acetic acid (25.9 mL, 453 mmol) and zinc powder (0.463 mL, 50.3 mmol). The cloudy maroon reaction mixture was capped and stirred for 60 min at 70° C. The reaction mixture was filtered through Celite and washed with MeOH. The residual filtrate was concentrated in vacuo, then partitioned between EtOAc (2×300 ml) and saturated aqueous NaHCO3 (350 ml). The combined organic layers were dried over Na2SO4 and concentrated. Reaction was purified using Biotage and eluted with 0-50% EtOAc/Heptane. Collected fractions and removed solvent in vaccuo, affording the title compound, 4-(benzylthio)-N-(4′-chloro-2-fluoro-5-methoxy-3′-methyl-[1,1′-biphenyl]-4-yl)benzene-1,2-diamine (1.87 g, 3.90 mmol, 78% yield). m/z (ESI) 480.2 (M+H)+.

Workup

  1. customThe cloudy maroon reaction mixture
  2. customwas capped
  3. filtrationThe reaction mixture was filtered through Celite
  4. washwashed with MeOH
  5. concentrationThe residual filtrate was concentrated in vacuo
  6. custompartitioned between EtOAc (2×300 ml) and saturated aqueous NaHCO3 (350 ml)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. concentrationconcentrated
  9. customReaction
  10. customwas purified
  11. washeluted with 0-50% EtOAc/Heptane
  12. customCollected fractions and removed solvent in vaccuo

Sources & evidence

ORD record
ord-2ed430482acf4eef894592ee18518a44
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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