4-Methylmorpholine → HCID 86722594, compound

HRID 1503070Notes

Reaction equation

HRID 1503070 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](Cl)=[O:11])=[C:8]([C:15]([F:18])([F:17])[F:16])[CH:7]=1.[F:30][C:31]([F:39])([F:38])[CH2:32][CH2:33][C:34]([NH:36][NH2:37])=[O:35].CN1CCOCC1>ClCCCl.O>[F:1][C:2]([F:29])([F:28])[CH:3]([C:19]1[CH:20]=[C:21]([Cl:27])[C:22]([Cl:26])=[C:23]([Cl:25])[CH:24]=1)/[CH:4]=[CH:5]/[C:6]1[CH:14]=[CH:13][C:9]([C:10]([NH:37][NH:36][C:34](=[O:35])[CH2:33][CH2:32][C:31]([F:39])([F:38])[F:30])=[O:11])=[C:8]([C:15]([F:16])([F:18])[F:17])[CH:7]=1

Participants

6

Reactant 3

HCID 79724-MethylmorpholineHCID 65712705HCID 65712705, compoundHCID 86722595HCID 86722595, compound

Product 1

HCID 86722594HCID 86722594, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Procedure

To a stirred solution of (E)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoyl chloride (143 mg, 0.288 mmol) in DCE (3 mL) were added 4,4,4-trifluorobutanehydrazide (45 mg, 0.29 mmol), and 4-methylmorpholine (63.4 μL, 0.577 mmol), and the resultant reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with water and extracted with EtOAc (3×30 mL). The combined EtOAc layers were washed with aqueous 1M HCl (−1×30 mL), saturated aqueous NaHCO3 (1×30 mL), and brine. The resulting organic solution was dried over Na2SO4 and concentrated under reduced pressure. Purification by automated flash column chromatography (SiO2, hexanes and EtOAc) afforded the title compound as a beige solid (78 mg, 42%): 1H NMR (400 MHz, CDCl3) δ 10.23 (s, 1H), 9.85 (s, 1H), 7.70-7.62 (m, 1H), 7.55 (dd, J=8.0, 1.6 Hz, 1H), 7.51 (d, J=8.0 Hz, 1H), 7.41 (s, 2H), 6.59 (d, J=15.9 Hz, 1H), 6.44 (dd, J=15.9, 7.8 Hz, 1H), 4.19-4.05 (m, 1H), 2.51 (dd, J=9.0, 6.6 Hz, 2H), 2.37-2.18 (m, 2H); 19F NMR (376 MHz, CDCl3) δ −59.46, −67.07, −68.59; ESIMS m/z 615 ([M−H]−).

Workup

  1. customthe resultant reaction mixture
  2. extractionextracted with EtOAc (3×30 mL)
  3. washThe combined EtOAc layers were washed with aqueous 1M HCl (−1×30 mL), saturated aqueous NaHCO3 (1×30 mL), and brine
  4. dry with materialThe resulting organic solution was dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customPurification by automated flash column chromatography (SiO2, hexanes and EtOAc)

Sources & evidence

ORD record
ord-99eceac841db489cac05c1460cba8b66
Source dataset
uspto-grants-2015_12
Patent number
US09211281B2

Reaction notes

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