Acetic Acid → 3'-(Ethylsulfonyl)-2-(2-fluoro-5-methylpyridin-3-yl)-4-methyl-5-(trifluoromethyl)biphenyl-3-amine

HRID 1882223Notes

Reaction equation

HRID 1882223 reaction equation
[CH2:1]([S:3]([C:6]1[CH:7]=[C:8]([C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[C:15]([CH3:22])=[C:14]([N+:23]([O-])=O)[C:13]=2[C:26]2[C:27]([F:33])=[N:28][CH:29]=[C:30]([CH3:32])[CH:31]=2)[CH:9]=[CH:10][CH:11]=1)(=[O:5])=[O:4])[CH3:2].CC(O)=O>[Fe].O>[CH2:1]([S:3]([C:6]1[CH:7]=[C:8]([C:12]2[CH:17]=[C:16]([C:18]([F:19])([F:20])[F:21])[C:15]([CH3:22])=[C:14]([NH2:23])[C:13]=2[C:26]2[C:27]([F:33])=[N:28][CH:29]=[C:30]([CH3:32])[CH:31]=2)[CH:9]=[CH:10][CH:11]=1)(=[O:5])=[O:4])[CH3:2]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 249640503-(3'-(Ethylsulfonyl)-4-methyl-3-nitro-5-(trifluoromethyl)biphenyl-2-yl)-2-fluoro-5-methylpyridine

Product 1

HCID 249637043'-(Ethylsulfonyl)-2-(2-fluoro-5-methylpyridin-3-yl)-4-methyl-5-(trifluoromethyl)biphenyl-3-amineYield 83.1%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-(3′-(ethylsulfonyl)-4-methyl-3-nitro-5-(trifluoromethyl)biphenyl-2-yl)-2-fluoro-5-methylpyridine (6.4 g, 13.3 mmol), iron (3.7 g, 66.3 mmol), HOAc, (32 mL), and H2O (11 mL) was heated at 80° C. for 2 h. After completion the reaction was concentrated in vacuo. The residue was reconstituted in dichloromethane (100 mL), filtered, and rinsed with dichloromethane (3×30 mL). The organic phase was washed with sat. NaHCO3 (1×100 mL) and brine (1×50 mL), dried (MgSO4), filtered, and concentrated in vacuo. Purification by silica gel chromatography (1:1 hexanes/EtOAc) gave 5.0 g (83%) of the title compound as a tan solid. 1H NMR (400 MHz, DMSO-d6): δ 7.93 (s, 1H), 7.67-7.7.71 (m, 2H), 7.53 (t, 1H), 7.46-7.48 (m, 1H), 7.42 (s, 1H), 6.93 (s, 1H), 5.09 (s, 2H), 3.11 (q, 2H), 2.27 (s, 3H), 2.21 (s, 3H), 0.85 (t, 3H). MS (ES) [m+H] calc'd for C22H20F4N2O2S, 453; found 453.3.

Workup

  1. concentrationAfter completion the reaction was concentrated in vacuo
  2. filtrationfiltered
  3. washrinsed with dichloromethane (3×30 mL)
  4. washThe organic phase was washed with sat. NaHCO3 (1×100 mL) and brine (1×50 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by silica gel chromatography (1:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-5489f2271c5a4c00ba442615664f19f0
Source dataset
uspto-grants-2012_11
Patent number
US08318939B2

Reaction notes

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