Hydrochloric Acid → HCID 107623903, compound

HRID 523220Notes

Reaction equation

HRID 523220 reaction equation
[Br:1][C:2]1[C:3]([CH3:9])=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[F:10][C:11]1[CH:22]=[CH:21][C:14]2[NH:15]C(=O)[O:17][C:18](=O)[C:13]=2[CH:12]=1.C[Al](C)C.Cl>C1(C)C=CC=CC=1>[NH2:15][C:14]1[CH:21]=[CH:22][C:11]([F:10])=[CH:12][C:13]=1[C:18]([NH:5][C:4]1[CH:6]=[CH:7][CH:8]=[C:2]([Br:1])[C:3]=1[CH3:9])=[O:17]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1235383-Bromo-o-toluidineHCID 2885605-Fluoroisatoic anhydrideHCID 16682925Trimethylaluminum

Product 1

HCID 107623903HCID 107623903, compoundYield 34.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A mixture of 3-bromo-2-methylaniline (1.50 g, 8.06 mmol) and 6-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione (1.46 g, 8.06 mmol) in toluene (40 mL) was cooled on an ice-water bath and treated portionwise with 2 M trimethylaluminum in toluene (10.1 mL, 20.2 mmol). The mixture was stirred at room temperature for 30 min, then was heated at 70° C. overnight. The mixture was cooled to 0° C., carefully treated with 1M aqueous HCl, and extracted 3 times with EtOAc. The combined organic phases were washed sequentially with saturated aqueous NaHCO3 and water, dried and concentrated. The residue was subjected to column chromatography on silica gel (120 g), eluting with EtOAc-hexanes (gradient from 5-40%), to provide 2-amino-N-(3-bromo-2-methylphenyl)-5-fluorobenzamide (0.893 g, 87% purity, 30% yield). Mass spectrum m/z 323, 325 (M+H)+. 1H NMR (400 MHz, MeOH-d4) δ 7.54 (1H, dd, J=8.03, 0.99 Hz), 7.48 (1 H, dd, J=9.68, 3.08 Hz), 7.33 (1 H, d, J=7.26 Hz), 7.16 (1 H, t, J=7.92 Hz), 7.04-7.12 (1 H, m), 6.83 (1 H, dd, J=9.02, 4.62 Hz), 2.39 (3 H, s).

Workup

  1. temperaturewas cooled on an ice-water bath
  2. temperaturewas heated at 70° C. overnight
  3. temperatureThe mixture was cooled to 0° C.
  4. extractionextracted 3 times with EtOAc
  5. washThe combined organic phases were washed sequentially with saturated aqueous NaHCO3 and water
  6. customdried
  7. concentrationconcentrated
  8. washeluting with EtOAc-hexanes (gradient from 5-40%)

Sources & evidence

ORD record
ord-a5261b53964a4efd8502824316b31490
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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