1-N-CBZ-3-HYDROXY-PIPERIDINE

To a solution 5-A (10.00 g, 73 mmol) in THF/H10 Step 4: preparation of 3-Hydroxy-piperidine-1-carboxylic acid benzyl ester. Tosuspension of piperidin-3-ol hydrochloride (134 g, 0.974 mol) and triethylamine (276 mL, 1.98 mol) in dichloromethane (2 L) at 0 °C was added a solution of benzyl chloroformate (140 mL, 0.981 mol) in dichloromethane (100 mL) drop wise over 2.5 h. The reaction was allowed to stir for an additional 30 mm at 0 °C, then allowed to warm15 to ambient temperature over 16 h, after which it was quenched with 1 N hydrochloric acid (3 L) and allowed to stir for 30 mm. The organic layer was separated, dried over sodium sulfate, and concentrated in vacuo to afford the title compound (218 g, 95 percent).1H-NMR (CDCI3) 67.29-7.41 (m, 5H), 5.14 (s, 2H), 3.59-3.85 (m, 3H), 3.13-3.27 (m, 2H), 2.18 (bs, 1H), 1.74-1.94 (m, 2H), 1.38-1.61 (m, 2H).A solution of 20.0 g of 5-chloro-2-hydroxypentylamine hydrochloride ((1-2)) in 50 mL of water was added dropwise with a solution of 20.4 g of sodium hydroxide in 20 mL of water at 10-15 ° C for about 1 hour .After dropping, the reaction was carried out at about 15 ° C for 2 hours.Then heated to 40-50 ° C for 4 hours.After the reaction was stopped, the mixture was cooled to room temperature, a solution of 80 mL of methylene chloride and 7.5 mL of sodium hydroxide in 20 mL of water was added, and then 20.0 g of benzyl chloroformate was added and the mixture was allowed to warm to room temperature and then allowed to react overnight.TLC plate, the reaction was complete, liquid separation, the aqueous phase was extracted once with 50mL of dichloromethane. The combined organic phases were washed with water, saturated brine, dried over anhydrous sodium sulfate, filtered off with suction and concentrated to give 25.0 g of colorless oil. The crude product was recrystallized from petroleum ether to give 21.9 g of N-benzyloxycarbonyl-3-hydroxypiperidine (3-1) as a white solid in a yield of 81percent.A solution of 20.0 g of 5-chloro-2-hydroxypentylamine hydrochloride ((1-2)) in 50 mL of water was added dropwise with a solution of 20.4 g of sodium hydroxide in 20 mL of water at 10-15 C for about 1 hour .After dropping, the reaction was carried out at about 15 C for 2 hours.Then heated to 40-50 C for 4 hours.After the reaction was stopped, the mixture was cooled to room temperature, a solution of 80 mL of methylene chloride and 7.5 mL of sodium hydroxide in 20 mL of water was added, and then 20.0 g of benzyl chloroformate was added and the mixture was allowed to warm to room temperature and then allowed to react overnight.TLC plate, the reaction was complete, liquid separation, the aqueous phase was extracted once with 50mL of dichloromethane. The combined organic phases were washed with water, saturated brine, dried over anhydrous sodium sulfate, filtered off with suction and concentrated to give 25.0 g of colorless oil. The crude product was recrystallized from petroleum ether to give 21.9 g of

Molecular Weight:235.28
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:235.12084340
Monoisotopic Mass:235.12084340
Topological Polar Surface Area:49.8
Heavy Atom Count:17
Complexity:251
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes