4-[3-(Methylsulfanyl)phenyl]-1-propyl-1,2,3,6-tetrahydro-pyridine synthesis

Yield:1025882-24-9 100%

Reaction Conditions:

with trifluoroacetic acid for 0.25 h;Product distribution / selectivity;Heating / reflux;

Steps:

4- (3-Methylsulfanyl-phenyl) -1-propyl-l, 2,3, 6-tetrahydro- pyridine (2)Chemical Formula: Ci₅H₂₁NSExact Mass: 247, 14 Molecular Weight: 247,4 m/z: 247,14 (100,0%), 248,14 (17,4%), 249,14 (4,7%), 249,15 (1 ,3%) Elemental Analysis: C, 72.82; H, 8.56; N, 5.66; S, 12.964- (3-Methylsulfanyl-phenyl) -l-propyl-piperidin-4-ol (1) (lOOmg, 0.38 mmol) was dissolved in 2 mL of trifluoroacetic acid (TFA) in a 50 mL flask while stirring in a nitrogen at- mosphere. The reaction mixture was heated to reflux on an isomantle. After 15 minutes the reaction mixture was cooled to room temperature. The TFA was removed by distillation under reduced pressure. The remaining brown oil was dissolved in diethyl ether, washed 3 times with water and once with brine. The aqueous layers and brine layer were collected, ba- sified with Na₂COa and extracted with diethyl ether twice. The organic layers were collected, dried on MgSO₄, filtered and the solvent was evaporated under reduced pressure using a rotavapor. Yield: 103 mg (111%). GCMS (EI): m/z 247 (M+), 218 (M-29); GC (100-320⁰C, 15°C/min) : 7.6 min. 4 - (3-Methanesulfonyl-phenyl) -1-propyl-l, 2, 3, 6 - t et r ahydr o-pyr idi ne-N-oxide (14, ACRl 6 -ene-N-oxide ) .A small amount (about 50 mg) of the Grignard reagent of 3- methylsulfanylbromobenzene was generated and was allowed to react with n-propyl-3-piperidone, forming 4- (3- methylsulfanyl-phenyl) -l-propyl-piperidin-4-ol, which was dehydrated in refluxing TFA and thereafter oxidized with mCPBA. The reaction mixture was applied to the top of a Pasteur pipette filled with neutral A12O3, eluting with about 10 mL CH2C12, 10 mL CH2C12:MeOH (40:1) and finally 10 mLCH2C12 :MeOH (20:1). The fractions containing nearly pure (>90%) 4- (3- methanesulfonyl-phenyl) -1-propyl-l, 2, 3, 6-tetrahydro-pyridine- N-oxide (14, MS API direct inlet showed M+l = 296.

References:

WO2008/127188,2008,A1 Location in patent:Page/Page column 19-20; 28