1,2-Dichloroethane → (E)-N-(1-(Methoxy(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide

HRID 1503794Notes

Reaction equation

HRID 1503794 reaction equation
[F:1][C:2]([F:29])([F:28])[CH:3]([C:19]1[CH:24]=[C:23]([Cl:25])[C:22]([Cl:26])=[C:21]([Cl:27])[CH:20]=1)/[CH:4]=[CH:5]/[C:6]1[CH:14]=[CH:13][C:9]([C:10](O)=[O:11])=[C:8]([C:15]([F:18])([F:17])[F:16])[CH:7]=1.ClCCCl.S(Cl)(Cl)=O.Cl.[NH2:39][C:40]1([C:43]([N:45]([O:51][CH3:52])[CH2:46][C:47]([F:50])([F:49])[F:48])=[O:44])[CH2:42][CH2:41]1>C(Cl)Cl>[CH3:52][O:51][N:45]([CH2:46][C:47]([F:48])([F:49])[F:50])[C:43]([C:40]1([NH:39][C:10](=[O:11])[C:9]2[CH:13]=[CH:14][C:6](/[CH:5]=[CH:4]/[CH:3]([C:19]3[CH:20]=[C:21]([Cl:27])[C:22]([Cl:26])=[C:23]([Cl:25])[CH:24]=3)[C:2]([F:28])([F:29])[F:1])=[CH:7][C:8]=2[C:15]([F:18])([F:16])[F:17])[CH2:42][CH2:41]1)=[O:44]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 24386Thionyl ChlorideHCID 867225822-(trifluoromethyl)-4-[(E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl]benzoic acidHCID 867226051-amino-N-methoxy-N-(2,2,2-trifluoroethyl)cyclopropanecarboxamide hydrochloride

Product 1

HCID 86722604(E)-N-(1-(Methoxy(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamideYield 8.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A 25 mL rb flask was charged with (E)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoic acid (150 mg, 0.31 mmol) and DCE (5 mL). Thionyl chloride (41.1 mg, 0.35 mmol) was added neat in one portion and the resulting reaction mixture was heated at reflux for 1.5 h. After which time, reaction mixture was allowed to cool and concentrated to give a brown oil which was used without further purification. The crude acid chloride was taken up in anhydrous DCM (2 mL) and was added drop wise to a cold solution containing crude 1-amino-N-methoxy-N-(2,2,2-trifluoroethyl)cyclopropanecarboxamide hydrochloride (78 mg, 0.31 mmol), TEA (66.7 mg, 0.66 mmol) and DCM (10 mL). The reaction mixture was stirred at RT for 18 h. The reaction mixture was diluted with DCM and washed with 0.1N HCl, aqueous NaHCO3, dried over MgSO4, filtered and evaporated to give an oil. The residue was chromatographed on a silica gel column eluting with 10% EtOAc/hex to afford the title compound (17 mg, 8.%): 1H NMR (400 MHz, CDCl3) δ 7.66 (dd, J=14.1, 1.6 Hz, 1H), 7.59 (dd, J=8.0, 1.8 Hz, 1H), 7.53 (d, J=8.0 Hz, 1H), 7.41 (s, 2H), 6.62 (d, J=15.9 Hz, 1H), 6.53 (s, 1H), 6.44 (m, 1H), 4.29 (q, J=8.5 Hz, 2H), 4.12 (m, 1H), 3.78 (s, 3H), 1.62 (m, 2H), 1.29 (m, 2H); 19F NMR (376 MHz, CDCl3) δ −58.81, −68.59, −69.22; ESIMS m/z 671.3 ([M−H]−).

Workup

  1. customthe resulting reaction mixture
  2. temperaturewas heated
  3. temperatureat reflux for 1.5 h
  4. customAfter which time, reaction mixture
  5. temperatureto cool
  6. concentrationconcentrated
  7. customto give a brown oil which
  8. customwas used without further purification
  9. additionwas added drop wise to a cold solution
  10. washwashed with 0.1N HCl, aqueous NaHCO3
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. customevaporated
  14. customto give an oil
  15. customThe residue was chromatographed on a silica gel column
  16. washeluting with 10% EtOAc/hex

Sources & evidence

ORD record
ord-7caaabf5c24f4963bf7bfc5e6a3d2ba2
Source dataset
uspto-grants-2015_12
Patent number
US09212164B2

Reaction notes

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