2-Bromo-4-fluoroaniline → HCID 12991542, compound

HRID 2190026Notes

Reaction equation

HRID 2190026 reaction equation
C[Al](C)C.[Br:5][C:6]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:7]=1[NH2:8].[N:14]1([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19][CH2:18][CH:17]=[C:16]([C:20](OC)=[O:21])[CH2:15]1>C(Cl)Cl>[Br:5][C:6]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:7]=1[NH:8][C:20]([C:16]1[CH2:15][N:14]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19][CH2:18][CH:17]=1)=[O:21]

Participants

5

Reactant 3

HCID 2428732-Bromo-4-fluoroanilineHCID 111284441-Tert-butyl 3-methyl 1,2,5,6-tetrahydropyridine-1,3-dicarboxylateHCID 16682925Trimethylaluminum

Product 1

HCID 12991542HCID 12991542, compoundYield 50.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Trimethylaluminium (2.0 M in hexanes, 3.98 mL, 7.96 mmol) was added dropwise to a solution of 2-bromo-4-fluoroaniline (1.26 g, 6.63 mmol) in DCM (15 mL) under N2. After gas evolution ceased, 1-tert-butyl 3-methyl 5,6-dihydropyridine-1,3(2H)-dicarboxylate (1.60 g, 6.63 mmol) in DCM (10 mL) was added and the resulting mixture was refluxed overnight. After cooling to about 0° C., the reaction was quenched by the addition of saturated aqueous NaHCO3 solution. The organic layer was separated. The aqueous phase was extracted with DCM. The combined organic layers were washed with brine, dried and concentrated. The residue was purified by column chromatography (hexanes:EtOAc, 6:1) to give tert-butyl 3-(2-bromo-4-fluorophenylcarbamoyl)-5,6-dihydropyridine-1(2H)-carboxylate (1.33 g, 50%) as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ 8.36 (dd, J=9.2, 6.0 Hz, 1H), 7.87 (br s, 1H), 7.32 (dd, J=7.6, 2.8 Hz, 1H), 7.07 (ddd, J=9.2, 6.0, 2.8 Hz, 1H), 6.82 (br s, 1H), 4.27 (s, 2H), 3.54 (t, J=6.0 Hz, 2H), 2.38 (m, 2H), 1.49 (s, 9H).

Workup

  1. temperaturethe resulting mixture was refluxed overnight
  2. customthe reaction was quenched by the addition of saturated aqueous NaHCO3 solution
  3. customThe organic layer was separated
  4. extractionThe aqueous phase was extracted with DCM
  5. washThe combined organic layers were washed with brine
  6. customdried
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (hexanes:EtOAc, 6:1)

Sources & evidence

ORD record
ord-25e87770f58245d69b9478bb34226f31
Source dataset
uspto-grants-2012_12
Patent number
US08324221B2

Reaction notes

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