1-Isopropylpiperidin-4-ol

A mixture of 4-hydroxypiperidine (10g, 0.10mol), acetone (21.8mL, 0.30mol), acetic acid (5.7mL, 0.10mol) and tetrahydrofuran (150mL) was stirred in an ice bath for 15 minutes. Preparation 3 1 -lsopropyl-piperidin-4-olA mixture of 4-hydroxypiperidine (1Og, O.IOmol), acetone (21.8ml, 0.30mol), acetic acid (5.7ml, O.IOmol) and tetrahydrofuran (150ml) was stirred in an ice bath for 15 minutes. Sodium triacetoxyborohydride (31.3g, 0.15mol) was then added portion wise and the mixture was stirred for a further 10 minutes. The reaction mixture was then warmed and stirred at room temperature for 10 minutes and at 40To a stirred solution of piperidin-4-ol (1 g, 9.87 mmol) in DCE (100 ml) under an atmosphere of nitrogen was added acetic acid (1.78 g, 29.7 mmol) and acetone (5.72 g, 98.7 mmol). The reaction mixture was stirred for 12 h at RT before addition of STAB (6.29 g, 29.7 mmol).After stirring for 12 h at RT the reaction mixture was concentrated at reduced pressure to give a white solid. Purification by FCC [SiOIntermediate 21: Methanesulfonic acid 1-isopropyl-piperidin-4-yl ester [] Step 1:; 4-Hydroxypiperidine (2.13g, 21.1mmol), K2CO3 (5.83g, 2eq.), 2-bromopropane (11.2g, 91 mmol, 4.3eq.) and MeOH (21.3ml) were refluxed together overnight. The reaction was allowed to cool to room temperature and quenched with 2M HCl solution (40ml) and extracted with TBME (40ml). The aqueous phase was basified to pH 14 with 2M NaOH solution and extracted with DCM (9 x 50ml). The combined organic extracts were dried over MgSO4, filtered, washed with DCM and concentrated in vacuo to give 1-isopropyl-4-hydroxypiperidine (2.41g, 80percentth) as a pale yellow oil.1H NMR (400MHz, CDCl3) δ3.67 (m, 1H), 2.85-2.66 (m, 3H), 2.33-2.20 (m, 2H), 1.99-1.38 (m, 5H), 1.04 (d, 6H).In a similar fashion (Rl, GP A) 2-bromopropane (1.46 g, 11.86 mmol), gave the title compound (0.5 g, 35percent yield) as oil after purification by FCC [SiO4-piperidinol (2.13 g, 21.1 mmol) was added to methanol (21 mL), and potassium carbonate (5.83 g, 42.2 mmol) and 2-bromopropane (11.2 g, 90.7 mmol) were further added thereto, followed by refluxing for 12 hours while stirring. Then, the reaction mixture was mixed with 2M HCl (40 mL) and extracted three times with dichloromethane (50 mL). The organic layer thus obtained was dried over anhydrous magnesium sulfate, and filtered and distilled under reduced pressure to obtain the title compound (2.2 g) as oil. [0331] To a cold (0° C.) solution of 1-isopropylpiperidone (purchased at Chemie Brunschwig AG, 100 g, 1.0 eq.) in ethanol (500 mL) was added sodium borohydride (19.3 g, 0.7 eq.) in small portions. To a cold solution of 1-isopropylpiperidone (purchased at Chemie Brunschwig AG, 100 g, 1.0 eq.) in ethanol (500 mL) was added sodium borohydride (19.3 g, 0.7 eq.) in small portions. Into a lOO-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 4-nitro-lH-pyrazole (565 mg, 4.997 mmol, 1 equiv), l-(propan-2-yl)piperidin-4- ol (715.67 mg, 4.997 mmol, 1.00 equiv), PPh3 (1572.66 mg, 5.996 mmol, 1.2 equiv), THF (50 mL). This was followed by the addition of DEAD (1131.24 mg, 6.496 mmol, 1.3 equiv) at 0C. The resulting solution was stirred for overnight at room temperature. The reaction was then quenched by the addition of 50 mL of water. The resulting solution was extracted with 2x100 mL of ethyl acetate concentrated. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (3:2). The collected fractions were combined and concentrated. This resulted in 670 mg (56.27%) of 4-(4-nitro-lH-pyrazol-l-yl)-l-(propan-2- yl)piperidine as a white solid. LC-MS (ES, m/z ): 239[M+l] +

Molecular Weight:143.23
XLogP3:0.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:143.131014166
Monoisotopic Mass:143.131014166
Topological Polar Surface Area:23.5
Heavy Atom Count:10
Complexity:95.4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes