N-Methoxy-N-methyl-4-(5-trifluoromethyl-isoxazol-3-yl)-benzamide → Cyclohexyl-[4-(5-trifluoromethyl-isoxazol-3-yl)-phenyl]-methanone

HRID 572273Notes

Reaction equation

HRID 572273 reaction equation
CON(C)[C:4](=[O:20])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[O:13][N:12]=2)=[CH:7][CH:6]=1.[CH:22]1([Mg]Br)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1>C1COCC1>[CH:22]1([C:4]([C:5]2[CH:6]=[CH:7][C:8]([C:11]3[CH:15]=[C:14]([C:16]([F:17])([F:18])[F:19])[O:13][N:12]=3)=[CH:9][CH:10]=2)=[O:20])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

4

Reactant 2

HCID 57606119N-Methoxy-N-methyl-4-(5-trifluoromethyl-isoxazol-3-yl)-benzamideHCID 178419651HCID 178419651, compound

Product 1

HCID 57606113Cyclohexyl-[4-(5-trifluoromethyl-isoxazol-3-yl)-phenyl]-methanoneYield 25.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of N-Methoxy-N-methyl-4-(5-trifluoromethyl-isoxazol-3-yl)-benzamide (Preparative Example 15, 300 mg, 1.0 mmol) in THF (10 mL) was treated with a 1 N THF solution of cyclohexylmagnesium bromide (4 mL, 4 mmol) and stirred for 2 hr then quenched with a saturated ammonium chloride solution (2 mL) and diluted with EtOAc (10 mL). The organic layer was then washed with brine (2×10 mL), dried over MgSO4, filtered, evaporated in vacuo and the residue chromatographed on silica gel with EtOAc/hexanes (5 then 10%) as eluant to afford product as a colorless solid (81 mg, 25%). 1H NMR (CDCl3) 1.26-1.58 (m, 5H), 1.74-1.94 (m, 5H), 3.23-3.32 (m, 1H), 7.09 (s, 1H), 7.79 (d, J=8.3, 2H), 7.87 (d, J=8.3, 2H). 19F NMR −64.6. LC/MS 7.79 min, [M+1]+ 324.

Workup

  1. customthen quenched with a saturated ammonium chloride solution (2 mL)
  2. additiondiluted with EtOAc (10 mL)
  3. washThe organic layer was then washed with brine (2×10 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customthe residue chromatographed on silica gel with EtOAc/hexanes (5

Sources & evidence

ORD record
ord-cfdfddc8803b4151a2e27aa4acdfc0d9
Source dataset
uspto-grants-2015_05
Patent number
US09029397B2

Reaction notes

Loading…