1,2-Dichloroethane → 2-(4-bromo-2-fluorophenyl)-N-(4-((dimethylamino)methyl)-3-(trifluoromethyl)phenyl)acetamide

HRID 576224Notes

Reaction equation

HRID 576224 reaction equation
[CH3:1][N:2]([CH2:4][C:5]1[CH:11]=[CH:10][C:8]([NH2:9])=[CH:7][C:6]=1[C:12]([F:15])([F:14])[F:13])[CH3:3].Cl.[Br:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25](O)=[O:26])=[C:20]([F:28])[CH:19]=1.CCN(CC)CC.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl>[Br:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25]([NH:9][C:8]2[CH:10]=[CH:11][C:5]([CH2:4][N:2]([CH3:1])[CH3:3])=[C:6]([C:12]([F:14])([F:13])[F:15])[CH:7]=2)=[O:26])=[C:20]([F:28])[CH:19]=1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 140537922-(4-Bromo-2-fluorophenyl)acetic acidHCID 57431457853297-25-3

Product 1

HCID 904163212-(4-bromo-2-fluorophenyl)-N-(4-((dimethylamino)methyl)-3-(trifluoromethyl)phenyl)acetamideYield 66.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 4-((dimethylamino)methyl)-3-(trifluoromethyl)aniline, 2 hydrochloride (4 g, 13.74 mmol), 2-(4-bromo-2-fluorophenyl)acetic acid (3.20 g, 13.74 mmol) and Et3N (9.57 mL, 68.7 mmol) in DCM (100 mL) stirred under a N2 atmosphere at 20° C. were added EDC (2.63 g, 13.74 mmol) and HOBt (2.104 g, 13.74 mmol) in one charge. The reaction mixture was stirred at 20° C. for 2 h. Then the solution was concentrated and distributed between EA and saturated NaHCO3 solution. The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=3:1). All fractions found to contain product by TLC (PE/EA=2:1, Rf 0.6) were combined and concentrated to yield a light yellow solid of 2-(4-bromo-2-fluorophenyl)-N-(4-((dimethylamino)methyl)-3-(trifluoromethyl)phenyl)acetamide (5.5 g, 9.14 mmol, 66.5% yield): 1H NMR (400 MHz, CDCl3) δ 7.79 (br. s., 2H), 7.70 (d, J=5.02 Hz, 2H), 7.30 (br. s., 2H), 3.73 (s, 2H), 3.53 (s, 2H), 2.47 (s, 6H); ES-LCMS m/z 435.0 (M+H).

Workup

  1. additioncharge
  2. concentrationThen the solution was concentrated
  3. extractionThe combined organic extract
  4. washwas washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by silica column chromatography (PE/EA=3:1)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-e75cdb6b69704e15a78935c140a9b2a9
Source dataset
uspto-grants-2015_05
Patent number
US09035063B2

Reaction notes

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