1-Piperidinecarboxylic acid, 4-acetyl-, 1,1-dimethylethyl ester

To the solution of 11 (43.2, 158 mmol) in THF (1.3 L) at -78 °C was added methylmagnesium bromide (106 mL, 3 M, 317 mmol) dropwise. The solution was warmed to 0 °C for 1 h before it was quenched with a saturated ammonium chloride solution. To this mixture was added EtOAc (1000 mL) and the organic phase was washed with brine (500 mL x 2), dried over Na2SO4 to give 12 (34.8 g, 96percent) as an oil.[0212] Tert-butyl-4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (2.29 g, 8.32 mmol) was dissolved in 30 ml of tetrahydrofuran (THF) and the resulting solution was cooled to -78 °C. b) f erf-butyl 4-acetylpiperidine-1-carboxylate Methyl magnesium bromide (3M in dietyhl ether, 2.45 ml_, 7.35 mmol) was dropwise added to an ice-cooled solution of the title compound of Preparation 55a (1g, 3.67 mmol) under argon and the mixture was stirred at that temperature for 18 hours. The reaction was quenched by the addition of ice and vigorously stirred for 30 minutes. The mixture was extracted with ethyl acetate, washed with brine and dried over sodium sulphate. The solvent was removed under reduced pressure and the residue was purified by column chromatography on silica flash, using hexane/ethyl acetate (1:1) as eluents, to yield the title compound (680 mg, 82percent) as colourless oil.[00191] Step 2: A 3- neck, 250 mL round bottom flask was charged with a solution of tert-bvXyl 4-(methoxy(methyl)carbamoyl)piperidine-l-carboxylate (9.9 g) in Et[00191] Step 2: A 3- neck, 250 mL round bottom flask was charged with a solution of tert-bvXyl 4-(methoxy(methyl)carbamoyl)piperidine-l-carboxylate (9.9 g) in EtINTERMEDIATE B5 foert-ButyM-acetylpiperidine-l-carboxylateK>i A 3 M solution of bromo(methyl)magnesium in diethylether (13.8 niL, 41.4 mmol) was cooled in an ice-bath and a solution of tert-butyi 4-{[methoxy(methyl)amino]carbonyl}- piperidine-1-carboxylate (Intermediate B4; 5.2 g 19.2 mmol) in EtTo a solution of Compound 2 (500 mg, 1.84 mmol) in anhydrous THF (5 mL) was added CMgBr (0.8 mL, 2.4 mmol) at 0 [0269] To a stirred solution of tert-butyl 4-(methoxy(methyl)carbamoyl)piperidine-l- carboxylate (4.3 g, 15.8 mmol) in dry THF (20 mL) was added a solution of methyl magnesium bromide (20 mL, 23.71 mmol, 1.6 M in THF:toluene) at -78 °C and the reaction was stirred at -78 °C for 2 h and RT for 2 h. The progress of the reaction was monitored by TLC. After complete consumption of starting material, the reaction was quenched with saturated NHTo a solution of tert-butyl 4-(methoxy(methyl)carbamoyl)piperidine-1- carboxylate (10.0 g, 36.76 mmol) in THF (150 mL) was added MeMgBr (24.5 mL, 73.52 mmol) at -78 C. The mixture was stirred at 25 C for 16 h.. TLC showed the reaction worked well. The mixture was quenched with aq. NHIn a 100 mL round-bottomed flask filled with a solution of 6.0 M NaOH (50 mL) was added 6 (9.00 g 30.2 mmol). The reaction mixture was heated under reflux for 20 h, then diluted with 300 mL water and was quenched by addition 240 mL dichloromethane. The collected organic layers were washed with brine and dried over sodium sulfate. The solvent was removed under reduced pressure, affording 6.42 g (94.0 percent yield) light yellow liquid.

Molecular Weight:227.30
XLogP3:1.3
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:227.15214353
Monoisotopic Mass:227.15214353
Topological Polar Surface Area:46.6
Heavy Atom Count:16
Complexity:273
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes