1-Boc-4-(2-hydroxyethyl)piperidine

The above resulting product (639mg, 2.4mmol) dissolved in 6ml of methanol, Underargon added the argon was replaced with hydrogen three times and reaction was carried out overnightin a hydrogenation apparatus (4 atm H2). The reaction solution was filteredthrough celite and washed with ethyl acetate. The filtrate was concentrated andseparated by column chromatography to give a white solid, 722 mg, 100percent yield. theabove resulting product(506mg, 1.9mmol) dissolved in 10ml of ether, reaction was colled down to -20 ° C, added diisobutylaluminum hydride(1.0M, 5mL, 5mmol), reaction was carried out for 10 minutes until the starting material disappeared. Then Poured into saturated sodium potassium tartrate solution, stirred at room temperature for 3 hours to clarify the reaction mixture, the aqueous phase was extracted three times with ether and the organic phases were combined and washed with saturated NaClsolution and dried over NaTo a solution of tert-butyl 4- (2-ethoxy-2-oxoethyl) piperidine-1-carboxylate (22 g, 81 mmol) in dry THF (100 mL) at -78 under NIntermediate 2 (500 mmol), 10percentPd/C, THF (1000 mL) was added to a 1 L hydrogenation reactor. Outside temperature 60°C, Reaction under 2.0MPa pressure for 10h, Stop the reaction, filter, Intermediate 3 in THF was obtained. Lithium borohydride (1000 mmol) is added, 21h reflux reaction, Stop the reaction, Cool down to 5~10°C 30percent aqueous HCl solution (200 mL) was added in sequence. 20percent aqueous HCl solution (200 mL), Stir 1h, Extract with ethyl acetate (200mL×3) Combine the ethyl acetate layers, Followed by water (100mL×2), Saturated brine (100mL × 2) wash, Drying with anhydrous sodium sulfate, filter, Concentrated to give 108 g of a white solid (Intermediate 4), The two-step yield was a total of 94percent.To a stirred solution of 2-piperidin-4-ylethanol (25.5 g, 197 mmol) in tetrahydrofuran (250 mL) was added di-tert-butyl dicarbonate (43.0 g, 197 mmol) at room temperature. 3.25 1-tert-Butyloxycarbonyl-4-hydroxyethyl-piperidine (61KS82) To a solution of 2-(piperidin-4-yl)ethanol (2.42 g, 18.7 mmol) in dichloromethane (24 mL) was added under nitrogen at 0 °C di-tert-butyl dicarbonate (4.09 g, 4.35 mL, 18.7 mmol). There was a strong gas evolution The solution was stirred at 0 °C for 15 min and at room temperature for 4 h. The reaction mixture was washed with water (50 mL), potassium hydrogen sulfate (10percent aqueous solution, 50 mL) and brine (50 mL). The aqueous layers were back-extracted with dichloromethane (50 mL). The combined organic layers were dried over sodium sulfate to yield colorless oil (4.1 g, 95 percent). MS: m/z = 230.5 (M+H)2-(N-tert-Butoxycarbonyl-4-piperidinyl)ethanol 2-(4-Piperidinyl)ethanol (1.0 g, 7.7 mmol) was dissolved in methanol (50 ml). To this solution, di-tert-butyl carbonate (2.0 g, 9.3 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After the reaction was confirmed by TLC to be complete, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:acetone=9:1) to obtain N-tert-butoxycarbonyl-2-(4-piperidinyl)ethanol (1.68 g, yield: 95percent).2-(Piperidin-4-yl)ethan-1-ol (3.00 g, 23.22 mmol) was dissolved in 30 mL dichloromethane. Di-tert-butyl dicarbonate (5.22 g, 23.92 mmol) was slowly added portionwise at 15 to 20° C. After that, the reaction mixture was stirred for 20 h at room temperature. The reaction mixture was slowly poured into 50 mL water after the reaction was complete as monitored by TLC. Then, the mixture was extracted with dichloromethane (50 mL×2). The combined organic layer was dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under vacuum to give a residue. The residue was purified by column chromatography (Height: 250 mm, Diameter, 20 mm, 100-200 slica gel, petroleum/ethyl acetate=3:1, 1:1) to afford 2-(1-tert-butoxycarbonyl-4-piperidyl)ethanol (4.89 g, 91.83percent yield) as a colorless liquid.To an ice-cold solution of 4-(2-hydroxyethyI) piperidine (4.25 g, 33 mmol) in CHTo A solution of 2- (4-PIPERIDYL) ETHANOL (9. 63 G, 74. 5 MMOL) IN DMF (100 ML) AT 0 C, DI-TERT-BUTYL DICARBONATE (16. 26 g, 5 mol) was added slowly. The mixture was stirred overnight at room temperature. The solvent was concentrated and the residue was dissolved in A mixture of ETOAC and water. The phases were separated. The organic phase was dried over NA2S04 and concentrated to dryness, to afford 15.09 g of the desired product : 88percent).To a stirred solution of 2-(piperidin-4-yl)ethanol (LXX, lg, 7.72 mmol) in tetrahydrofuran and water mixture (40 mL, 1 : 1) was added sodium bicarbonate (1.62 g, 19.32 mmol) and Boc anhydride (2.6 mL, 11.6 mmol) at room temperature and stirred for 3 h. The reaction mixture was diluted with ethyl acetate and the organic portion was washed with water and brine, dried over sodium sulphate and concentrated under reduced pressure to get the crude product which was purified by flash column chromatography using ethylacetate-hexane gradient to afford the titled product as gummy solid (LXXI, 1.6 g, 88 percent). LC-MS m/z calcd for C12H23NO3, 229.2; found 130.2 [M-Boc]+.A mixture of 4-piperidin ethanol (2. 0 g, 15 mmol, 1.0 eq. ) and t-butyl dicarbonate (3. 87 ML, 18.5 MMOL, ). 2 eq. ) in anhydrous THF (80 mL) is kept under stirring at room temperature for one night. The solvent is then removed by evaporation under reduced pressure and the raw product obtained purified by flash chromatography using AcOEt : petroleum ether 60 : 40 as eluent mixture. 4-(2-Hydroxy-ethyl)-piperidine-1-carboxylic acid tert-butyl ester (37) is obtained as a colourless oil (3.1 G, 13.4 mmol, yield = 87percent) HPLC (method A) : Rt = 7.92 min. H1 NMR (No., CDCL3-D3, 300 MHz) : 1.14 (DQ, 2H, Hf, J=6. 3, 13. 5 Hz); 1.47 (S, 9H, C (CH3) 3) : 1. 55 (pt, 2H, Hc, J= 6.3 HZ) ; 1. 50-1.65 (m, 1H, Hc); 1.69 (d, 2H, Hd, J=13. 2 Hz); 1.89 (s, 1H, OH) ; 2.71 (LAD, 2H, Hb, J= 2. 1, 12.9 Hz) ; 3.73 (t, 2H, Hg, J= 6.3 Hz) ; 4.10 (m, 2H, Ha).(0.01 mol) of 4-piperidineethanol, 2.4 ml (0.02 mol) of triethylamine and 30 ml of dichloromethane were charged into a 150 ml three-necked flask. After cooling to 0 ° C, 2.54 g (0.01 mol) of di-t-butyl dicarbonate was slowly added dropwise. After completion of the reaction, the reaction was carried out at 25 ° C overnight. The reaction was terminated by the disappearance of the starting material by TLC (PE: EA = 2: 1). Dichloromethane was distilled off under reduced pressure, 40 ml of ethyl acetate was added thereto, and the mixture was washed with saturated brine, neutralized and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give 2.27 g (85.2percent) of a clear oil.[00482] To a stuffed solution of 2-(piperidin-4-yl)ethanol (30 g, 0.2322 mmol) in i, 2-dichloromethane (200 ml) was added in portions di-tert-butyl dicarbonate (53 g, 0.24 mmol) . The resultant mixture was stuffed at room temperature overnight. After confirming reaction completion by thin-layer chromatography, the reaction mixture was washed with water and concentrated to yield compound INT-1(52g).To a stirred solution of 2-(piperidin-4-yl)ethanol (30 g, 0.2322 mmol) in 1, 2-dichloromethane (200 ml) was added in portions di-tert-butyl dicarbonate (53 g, 0.24 mmol) . The resultant mixture was stirred at room temperature overnight. After confirming reaction completion by thin-layer chromatography, the reaction mixture was washed with water and concentrated to yield compound INT-1 (52g).Preparation of tert-butyl 4-(2-hydroxyethyl)piperidine- 1 -carboxylate (TNT-1):[00491] To a stirred solution of 2-(piperidin-4-yl)ethanol (30 g, 0.2322 mmol) in i, 2-dichloromethane (200 ml) was added in portions di-tert-butyl dicarbonate (53 g, 0.24 mmol) . The resultant mixture was stirred at room temperature overnight. After confirming reaction completion by thin-layer chromatography, the reaction mixture was washed with water and concentrated to yield compound INT-1 (52g).A solution (20 ml) of di-tert-butyl carbonate (8.95 g, 41.0 mmol) in tetrahydrofuran was added dropwise to a solution (80 ml) of 4-piperidineethanol (5.30 g, 41.0 mmol) in tetrahydrofuran at room temperature and stirred overnight. To a stirred solution of 2-(piperidin-4-yl)ethanol (30 g, 0.2322 mmol) in1 , 2-dichloromethane (200 ml) was added in portions di-tert-butyl dicarbonate (53 g, 0.24 mmol) . The resultant mixture was stirred at room temperature overnight. Afterconfirming reaction completion by thin-layer chromatography, the reaction mixturewas washed with water and concentrated to yield compound INT-l (52g).Step B

Molecular Weight:229.32
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:229.16779360
Monoisotopic Mass:229.16779360
Topological Polar Surface Area:49.8
Heavy Atom Count:16
Complexity:227
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes