Potassium Iodide → N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{(3-(1H-tetrazol-1-yl)-phenyl]oxy}acetamide

HRID 1809150Notes

Reaction equation

HRID 1809150 reaction equation
Cl[CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:7]=1)=[O:4].N[C:18]1[CH:19]=[C:20]([N:24]2[CH:28]=[N:27][N:26]=[N:25]2)[CH:21]=[CH:22][CH:23]=1.CN(C=[O:33])C.[I-].[K+]>C(OCC)(=O)C>[Cl:12][C:9]1[CH:10]=[CH:11][C:6]([NH:5][C:3](=[O:4])[CH2:2][O:33][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([N:24]3[CH:28]=[N:27][N:26]=[N:25]3)[CH:19]=2)=[CH:7][C:8]=1[C:13]([F:16])([F:15])[F:14]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 6228DimethylformamideHCID 8630073-(1H-1,2,3,4-tetrazol-1-yl)anilineHCID 23077292-chloro-N-[4-chloro-3-(trifluoromethyl)phenyl]acetamide

Product 1

HCID 4714043N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{(3-(1H-tetrazol-1-yl)-phenyl]oxy}acetamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a 50 mL recovery flask was added 2-chloro-N-(4-chloro-3-trifluoromethylphenyl)-acetamide (400 mg, 1.47 mmol, 1.0 eq.) and 1-(3-aminophenyl)-1H-tetrazole 11 (710 mg, 4.40 mmol, 3 eq.) and DMF (10 mL). A catalytic amount of potassium iodide was added. The reaction mixture was heated at 70° C. overnight. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with a succession of 10% aq. LiCl (3×50 mL) and sat'd aq. NaCl (50 mL). The combined aqueous phases were extracted with ethyl acetate (2×50 mL). The combined organic phases were dried over anhydrous Na2SO4, filtered, and concentrated to give a tan solid. The solid was recrystallized in methanol and acetonitrile (10:1) to give a white solid (63 mg). Subsequent crops were isolated from the mother liquor (91 mg). Total yield: 154 mg, 26%. LC/MSD (HP Series 1100 MSD) MS (ES+) m/z 397.1 (M+H)+1 1H-NM, Varian 400 MHz (DMSO-d6) δ 10.51 (s, 1H), 10.00 (s, 1H), 8.19 (d, 1H), 7.88-7.85 (dd, 1H), 7.65 (d, 1H), 7.34-7.30 (t, 1H), 7.09 (t, 1H), 7.05-7.03 (dd, 1H), 6.75 (dd, 1H), 6.74 (t, 1H), 4.00 (d, 2H) ppm.

Workup

  1. washwashed with a succession of 10% aq. LiCl (3×50 mL)
  2. extractionThe combined aqueous phases were extracted with ethyl acetate (2×50 mL)
  3. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a tan solid
  7. customThe solid was recrystallized in methanol

Sources & evidence

ORD record
ord-bce7dd2e273e4c64840dc15ab3d05cbf
Source dataset
uspto-grants-2013_01
Patent number
US08362017B2

Reaction notes

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