Reaction #2562

Reaction equation

sodium cyanoborohydride

N-Formylmethyl-3-methoxy-N-(2-methoxyphenyl)-benzamide

4-(4-fluorobenzoyl)piperidine

acetone

→

title compound

Yield 46.1%

N-{2-[4-(4-Fluorobenzoyl)piperidino]ethyl}-3-methoxy-N-(2-methoxyphenyl)benzamide

Yield 46.1%

Solvents

ether

methanol

Conditions

Workup

1. 1
   Otherat room temperature
2. 2
   workup.ADDITIONwas added to the above mixture
3. 3
   Filtrationfiltered through cerite, and the solvent
4. 4
   Otherwas removed by evaporation
5. 5
   workup.DISSOLUTIONThe thus obtained colorless oily residue was dissolved in ether (7 ml)
6. 6
   workup.ADDITIONmixed with saturated hydrogen chloride/ether solution (7 ml)
7. 7
   workup.STIRRINGstirred for 5 minutes
8. 8
   OtherAfter removing the ether layer
9. 9
   workup.ADDITIONthe reaction solution was mixed with water (7 ml) and potassium carbonate (1.5 g)
10. 10
    Extractionextracted with ether
11. 11
    Otherdried on potassium carbonate
12. 12
    Otherthe solvent was removed by evaporation
13. 13
    OtherThereafter, the resulting colorless oily residue was purified

Procedure

N-Formylmethyl-3-methoxy-N-(2-methoxyphenyl)-benzamide (141 mg, 0.473 mmol), and 4-(4-fluorobenzoyl)piperidine (125 mg, 0.60 mmol) were dissolved in methanol (4.5 ml) to which was subsequently added molecular sieve 4A (300 mg) at room temperature. After 1 hour of stirring at the same temperature, sodium cyanoborohydride (12 mg, 0.191 mmol) was added to the above mixture, followed by 45 minutes of stirring and subsequent addition of acetone (2 ml). The reaction solution was diluted with ether (15 ml) and filtered through cerite, and the solvent was removed by evaporation. The thus obtained colorless oily residue was dissolved in ether (7 ml), mixed with saturated hydrogen chloride/ether solution (7 ml) and stirred for 5 minutes. After removing the ether layer, the reaction solution was mixed with water (7 ml) and potassium carbonate (1.5 g) and extracted with ether and dried on potassium carbonate, and then the solvent was removed by evaporation. Thereafter, the resulting colorless oily residue was purified by subjecting it to a silica gel column chromatography (ether:hexane=3:2) to obtain 107 mg (46.1%) of the title compound in the form of light yellow oil.

Source