Dichloromethane → 6-(2-Trifluoromethyl-phenyl)-3-nitro-pyridin-2-ylamine

HRID 1191240Notes

Reaction equation

HRID 1191240 reaction equation
Br[C:2]1[N:7]=[C:6]([NH:8]C(C2ON=C(C(C)(C)C)C=2)=O)[C:5]([N+:20]([O-:22])=[O:21])=[CH:4][CH:3]=1.[F:23][C:24]([F:35])([F:34])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)Cl>COCCOC.O>[F:23][C:24]([F:35])([F:34])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:2]1[N:7]=[C:6]([NH2:8])[C:5]([N+:20]([O-:22])=[O:21])=[CH:4][CH:3]=1

Participants

7

Procedure

A solution of 3-tert-butyl-isoxazole-5-carboxylic acid (6-bromo-3-nitro-pyridin-2-yl)-amide (139 mg, 0.377 mmol, prepared as described in the previous step) in DME (15 mL) and water (5 mL) was treated with 2-trifluoromethylphenylboronic acid (85.8 mg, 0.452 mmol) and cesium carbonate (245 mg, 0.753 mmol). The resulting mixture was de-gassed via sonication, placed under Ar, treated with PdCl2(dppf).DCM (15.4 mg, 0.019 mmol), and heated to 80° C. for 18 h. The cooled mixture was diluted with water (50 mL) and extracted twice with EtOAc (50 mL, 25 mL). The combined extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 12-g SEPRA Si 50 SPE column (Isco system: Flow rate=15 mL/min; Eluent=EtOAc/hexanes, 1:99 v/v for 10 min, then 1:99 to 3:17 v/v over 40 min) to yield 6-(2-trifluoromethyl-phenyl)-3-nitro-pyridin-2-ylamine as a yellow solid. Mass Spectrum (LCMS, APCI pos.): Calculated for C12H8F3N3O2: 284.1 (M+H); Measured: 284.0.

Workup

  1. customThe resulting mixture was de-gassed via sonication
  2. additiontreated with PdCl2(dppf)
  3. extractionextracted twice with EtOAc (50 mL, 25 mL)
  4. dry with materialThe combined extracts were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified on a 12-g SEPRA Si 50 SPE column (Isco system

Sources & evidence

ORD record
ord-0e2d57474a69488683128239ee6b146e
Source dataset
uspto-grants-2014_03
Patent number
US08680098B2

Reaction notes

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