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

HRID 1050077Notes

Reaction equation

HRID 1050077 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][C:13]=1[C:19]([F:22])([F:21])[F:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][C:31](O)=[O:32])=[C:26]([F:34])[CH:25]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(CC)CC>C(Cl)Cl>[CH2:1]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:18]=[CH:17][C:15]([NH:16][C:31](=[O:32])[CH2:30][C:27]2[CH:28]=[CH:29][C:24]([Br:23])=[CH:25][C:26]=2[F:34])=[CH:14][C:13]=1[C:19]([F:20])([F:21])[F:22])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 140537922-(4-Bromo-2-fluorophenyl)acetic acidHCID 904168474-(2-Benzyloxyethoxy)-3-trifluoromethyl-phenylamine

Product 1

HCID 90416157N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-bromo-2-fluorophenyl)acetamideYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A suspension of 4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)aniline (668 mg, 2.146 mmol) in DCM (35 mL) was added to a solution of 2-(4-bromo-2-fluorophenyl)acetic acid (500 mg, 2.146 mmol) in DCM (35 mL). HOBt (493 mg, 3.22 mmol), EDC (617 mg, 3.22 mmol) and Et3N (0.897 mL, 6.44 mmol) and the mixture was at 26° C. for 3 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=10/1). All fractions found to contain product by TLC (PE/EA=5/1, Rf 0.6) were combined and concentrated to yield a light yellow solid of N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-bromo-2-fluorophenyl)acetamide (1 g, 1.900 mmol, 89.0% yield): 1H NMR (400 MHz, CD3OD) δ 7.83-7.82 (d, J=2.8 Hz, 1H), 7.33-7.24 (m, 10H), 4.83 (s, 1H), 4.23-4.21 (m, 2H), 3.84-3.83 (m, 2H), 3.71-3.67 (m, 2H); ES-LCMS m/z 525.9 (M+H).

Workup

  1. concentrationThen the solution was concentrated
  2. extractionThe combined organic extract
  3. washwas washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by silica column chromatography (PE/EA=10/1)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-fd7e63adaa6b44b291221163f22de266
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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