Potassium Carbonate → HCID 107623999, compound

HRID 523214Notes

Reaction equation

HRID 523214 reaction equation
S(Cl)(Cl)=O.[NH2:5][C:6]1[C:14]([CH3:15])=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([OH:10])=O.[Br:16][C:17]1[C:18]([CH3:24])=[C:19]([CH:21]=[CH:22][CH:23]=1)[NH2:20].C([O-])([O-])=O.[K+].[K+]>C1COCC1>[NH2:5][C:6]1[C:14]([CH3:15])=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([NH:20][C:19]1[CH:21]=[CH:22][CH:23]=[C:17]([Br:16])[C:18]=1[CH3:24])=[O:10]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 781012-Amino-3-methylbenzoic acidHCID 1235383-Bromo-o-toluidine

Product 1

HCID 107623999HCID 107623999, compoundYield 40.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of thionyl chloride (3.15 g, 26.5 mmol) and 2-amino-3-methylbenzoic acid (2.00 g, 13.23 mmol) in THF (50 mL) was heated at reflux for 2 h. The cooled mixture was concentrated and the residue was combined with 3-bromo-2-methylaniline (4.92 g, 26.5 mmol) in THF (50 mL) and heated at reflux for 5 h. The mixture was cooled to room temperature, treated with 10% aqueous K2CO3 and stirred at room temperature for 30 min. The resulting mixture was extracted 3 times with DCM, and the combined organic phases were washed with water, dried and concentrated. The residue was purified by column chromatography on silica gel (330 g), eluting with EtOAc-hexanes (gradient from 0-20%), to give 2-amino-N-(3-bromo-2-methylphenyl)-3-methylbenzamide as a yellow solid (1.71 g, 40% yield). Mass spectrum m/z 319, 321 (M+H)+. 1H NMR (400 MHz, chloroform-d) δ 7.70 (d, J=7.9 Hz, 1H), 7.64 (br. s., 1H), 7.50-7.40 (m, 2H), 7.24 (d, J=7.3 Hz, 1H), 7.14 (t, J=8.0 Hz, 1H), 6.70 (t, J=7.6 Hz, 1H), 5.67 (br. s., 2H), 2.44 (s, 3H), 2.23 (s, 3H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. concentrationThe cooled mixture was concentrated
  4. temperatureheated
  5. temperatureat reflux for 5 h
  6. extractionThe resulting mixture was extracted 3 times with DCM
  7. washthe combined organic phases were washed with water
  8. customdried
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography on silica gel (330 g)
  11. washeluting with EtOAc-hexanes (gradient from 0-20%)

Sources & evidence

ORD record
ord-f0974cf769684d65bb9be40243b57697
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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