Cyclohexanecarbonyl chloride → Cyclohexyl-[5-(4-methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophen-2-yl]-methanone

HRID 1514091Notes

Reaction equation

HRID 1514091 reaction equation
[CH3:1][C:2]1[C:3]([C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)=[N:4][O:5][C:6]=1[C:7]([F:10])([F:9])[F:8].[CH:16]1([C:22](Cl)=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1>ClCCl>[CH:16]1([C:22]([C:13]2[S:12][C:11]([C:3]3[C:2]([CH3:1])=[C:6]([C:7]([F:8])([F:10])[F:9])[O:5][N:4]=3)=[CH:15][CH:14]=2)=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

4

Reactant 2

HCID 75938Cyclohexanecarbonyl chlorideHCID 57606117HCID 57606117, compound

Product 1

HCID 25211092Cyclohexyl-[5-(4-methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophen-2-yl]-methanoneYield 35%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-Methyl-3-thiophen-2-yl-5-trifluoromethyl-isoxazole (Preparative Example 21, 468 mg, 2.0 mmol) in dichloromethane (20 mL) was treated with FeCl3 (324 mg, 2.0 mmol) followed by cyclohexylcarbonyl chloride (268 μL, 0.5. mmol). The reaction was heated at reflux for 20 hours followed by evaporation and partitioning between EtOAc (25 mL) and an aqueous 1N hydrochloric acid solution (25 mL). The organic portion was then washed with a second portion of 1N hydrochloric acid solution and brine, dried over MgSO4, filtered, and concentrated in vacuo to afford crude product. The crude product was then chromatographed on silica gel with EtOAc/hexanes (3%) as eluant to afford product as a colorless solid (240 mg, 35%). 1H NMR (CDCl3) 1.24-1.76 (m, 6 H), 1.84-1.94 (m, 4 H), 2.37 (d, J=1.3, 3 H), 3.05-3.15 (m, 1 H), 7.54 (d, J=4.0, 1 H), 7.74 (d, J=4.0, 1 H). 13C NMR 7.9, 25.9, 26.0, 29.7, 47.8, 114.8, 118.7 (q, J=271), 129.1, 131.6, 135.5, 146.0, 155.4 (q, J=41), 158.0, 196.8. 19F NMR −63.1. LC/MS 7.92 min, [M+1]+ 344.

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 20 hours
  3. customfollowed by evaporation
  4. custompartitioning between EtOAc (25 mL)
  5. washThe organic portion was then washed with a second portion of 1N hydrochloric acid solution and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford crude product
  10. customThe crude product was then chromatographed on silica gel with EtOAc/hexanes (3%) as eluant

Sources & evidence

ORD record
ord-a75f12c5e14a487a9888d5cbc4470270
Source dataset
uspto-grants-2012_07
Patent number
US08222243B2

Reaction notes

Loading…