3-Methylpiperidin-4-onehydrochloride

Preparation of acyl-chloride: A solution of 200 mg (0.571 mmol) of the compound from Example 52A in 4 mL of dichloromethane was initially treated at RT with 249 mu (2.86 mmol) of oxalyl chloride and then with a small drop of DMF.After the reaction mixture had been stirred at RT for 2.5 h, it was concentrated to dryness on a rotary evaporator.The remaining residue was dried under high vacuum and then reacted further in the next substep. Preparation of the amide: The acid chloride obtained above was dissolved in 1 ml of dichloromethane and added to a solution of 171 mg (1.14 mmol) of methyl 6-r(1-methylethyl)sulfonyll-3-r(3-methyl-4-oxo-1-piperidinyl)methyll-2-r3- (trifluoromethyl)phenyll-4-quinolinecarboxylateA suspension of methyl 3-methyl-6-[(1-methylethyl)sulfonyl]-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.25 g, 2.77 mmol), V-bromosuccinimide (0.641 g, 3.60 mmol), and benzoyl peroxide (0.067 g, 0.277 mmol) in carbon tetrachloride (27 ml) was heated to 100C for 19 h. The mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The residue was suspended in acetonitrile (20 mL), and Step 1: To a solution of racemic 3-methyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester in anhydrous DCM at 0 C., ethanolic-HCl was added slowly and the reaction mixture was allowed to stir at 25 C. for 3 h. TLC (hexanes/EtOAc 40% EtOAc) showed complete consumption of the starting material. The reaction mixture was evaporated to give racemic Step 2: To a suspension of the product of step 1 in DCM at 0 C., DIPEA (4 eqv) was added slowly and stirred for 30 minutes at 25 C. The reaction mixture was cooled again to 0 C. and acetyl chloride (1.1 eqv) was added slowly. The resulting mixture was stirred at 25 C. for 16 hrs before being quenched by addition of saturated aqueous NaHCO3. The aqueous layer was back extracted three times with DCM. The combined organics were washed with H2O, dried (Na2SO4), filtered and evaporated. The residue was purified by SiO2 flash chromatography to give racemic 1-acetyl-3-methyl-piperidin-4-one (94% over two steps).Preparation of 1-[1-(4, 4'-difluorodiphenylmethoxy)-propyl]-3-methylpiperidine-4-one Compound VI: {R1 and R2 =4-F, m=1, A=(CH2)n, n=3, R4, R5 and R6 =H, R3 =CH3 } The mixture of 1-[4, 4'-difluorodiphenylmethoxy]-3-chloropropane (12 g, 0.04M), Stage 15c:

Molecular Weight:149.62
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Exact Mass:149.0607417
Monoisotopic Mass:149.0607417
Topological Polar Surface Area:29.1
Heavy Atom Count:9
Complexity:101
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes