1-Benzyl-4-hydroxyMethylpiperidin-4-ol

A3a) 1-benzyl-4-hydroxymethyl-piperidin-4-ol A solution of 200 g AD-Mix-Alpha (Messrs Aldrich, Item no. 39, 275-8) in 500 mL water and 300 mL tert-butanol was stirred for 20 min at RT, cooled to 0° C., combined with 13.7 g (144 mmol) methanesulphonic acid amide and 27.0 g (144 mmol) of 1-benzyl-4-methylene-piperidine and, after removal of the cooling bath, stirred for 22 h at RT. 59 g NaA solution of the epoxide (1.33 g, 6.54 mmol) in aqueous 0.2 M sulfuric acid (82 mL) was stirred at room temperature for 20 hours. The solution was cooled to 0 °C, and sodium carbonate was added until the pH of the aqueous mixture reached 12. The mixture was then diluted with water (20 ML), and extracted with ethyl acetate (3x 200 ML). The combined organic layers were dried (magnesium sulfate), filtered, and concentrated under reduced pressure. The resulting white solid was purified via flash chromatography eluting with a gradient of dichloromethane : methanol (5: 1 to 1: 1) to deliver the title compound as a waxy solid (1.12 g, 77percent). MS (APCI) (M+1/Z) 221.1.A mixture of Compound 2 (30.5 g, 150 mmol) in HStep 1 4-(Hydroxymethyl)piperidin-4-ol hydrochloride 500 mg of step 1 4- (hydroxymethyl) piperidin-4-ol hydrochloride1-benzyl-4- (hydroxymethyl) piperidin-4-ol 500 mg (J. Med. Chem., was dissolved in ethanol 10ml synthesis) according to 1988, 486-491, 10% palladium-carbon 300mg and concentrated hydrochloric acid 0.38ml was added and overnight hydrogenated at room temperature.Insoluble matter was separated by filtration, and washed with ethanol and water, and the filtrate was concentrated under reduced pressure.To the residue was powdered addition of diethyl ether, the desired product was obtained 374mg as a white powder.60% sodium hydride (0.30 g) was added to a solution of the compound (1.66 g) obtained in Step 2 in anhydrous dimethylformamide (8 mL) under cooling with ice-water, and stirred at room temperature for thirty minutes under nitrogen atmosphere. 4-fluorobenzonitrile (0.91 g) was added to the mixture and stirred at room temperature for two days. The resulting mixture was poured into water (30 mL) and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (Chromatorex NH)(eluent; ethyl acetate : hexane = 1 : 1) to obtain the titled compound (2.2 g).A3a)

Molecular Weight:221.29
XLogP3:0.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:221.141578849
Monoisotopic Mass:221.141578849
Topological Polar Surface Area:43.7
Heavy Atom Count:16
Complexity:206
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes