1-(Phenylmethyl)-4-piperidinemethanol

Colorless liquid

1-Benzyl-4-(chloromethyl)piperidine 21 (Scheme 12) Thionyl chloride (0.01 mole) was added to an ice cold ester 40 (0.005 mole) and the resulting mixture was stirred at room temperature for 5 hours. The progress of the reaction was monitored by TLC. The reaction mixture was poured into ice cold water (50 ml). The mixture was extracted with ethyl acetate (25 ml*2), washed with water (25 ml), dried over anhydrous magnesium sulfate (Na2SO4) and evaporated the solvent. The residue was passed through a short silica gel column using 0-100percent ethyl acetate and hexane as eluent to give the pure chloride 21 as color less oil in 66percent yield (0.74 g).A stirred solution of (l-benzylpiperidin-4-yl) methanol (2.79 g, 13.7 mmol) and NEt3 (1.65 g, 16.3 mmol) in CH2Cl2 (50 ml) was cooled to 00C and a solution of napthoyl chloride(prepared as in Example 16) (3.11 g, 16.3 mmol) dissolved in CH2C12/THF (1:1 , 50 ml) was added dropwise. The resulting mixture was stirred at room temperature overnight, evaporated in vacuo and to the residue was added EtOAc (100 ml) . The organic layer was washed with water (50 ml) , brine(50 ml) and water (50 ml) . The organic layer was dried over Na2SO4, filtered and evaporated in vacuo to give an oil. The oil was separated with flash chromatography (SiO2, EtOAc) to give the expected product as a yellow oil (3.12 g, 63.3percent) . EPO Synthesis of 1- [ (l-benzylpiperidin-4-yl) carboxymethyl] napthalene A stirred solution of (1-benzylpiperidin-4-yl) methanol (2.79 g, 13.7 mmol) and NEt3 (1.65 g, 16.3 mmol) in CH2CI2 (50 ml) was cooled to 0 °C and dropwise added a solution of napthoyl chloride (prepared as in example 7) (3.11 g, 16.3 mmol) dissolved in CH2Cl2/THF (1: 1, 50 ml). The resulting mixture was stirred to room temperature overnight, evaporated in vacuo and the residue added EtOAc (100 ml). The organic layer was washed with water (50 ml), brine (50 ml) and water (50 ml). The organic layer was dried over Na2SO4, filtered and evaporated in vacuo to give an oil. The oil was separated with flash chromatography (SiOz, EtOAc) to give the expected product as a yellow oil (3.12 g, 63.3 percent). 1H-NMR (300 MHz, CDCl3) : 8 8.94 (d, 1 H), 8.22-8. 19 (m, 1 H), 8.04 (d, 1 H), 7.90 (d, 1 H), 7.64-7. 49 (m, 3 H), 7.49-7. 25 (m, 5 H), 4.30 (d, 2 H), 3.52 (s, 2 H), 2.98 (d, 2 H), 2.09-2. 00 (m, 2 H), 1.93-1. 83 (m, 3 H), 1.57-1. 45 (m, 2 H) MS (ES): 360.1 [M + H] +A suspension of LiAlH4 (1.52 g, 40.0 mmol) in dry THF (30 ml) was stirred at O0C and a solution of l-benzylpiperidin- 4-yl) ethylcarboxylate hydrochloride (2.47 g, 10.0 mmol) in dry THF (50 ml) was added dropwise. The obtained mixture was heated under reflux for 4 h and then cooled to room temperature. EtOAc (200 ml) , water (40 ml) , and a 2 N aqueous solution of NaOH (10 ml) were added. The obtained mineral precipitate was filtered through a pad of kieselguhr, the filtrate evaporated in vacuo and water (50 ml) added to the residue. The aqueous layer was extracted EPO Preparation of intermediate 1- [ (l-benzylpiperidin-4-yl) methanol A suspension of LiAIH4 (1.52 g, 40.0 mmol) in dry THF (30 ml) was stirred at 0 °C and dropwise added a solution of 1-benzylpiperidin-4-yl) ethylcarboxylate hydrochloride (2. 47 g, 10.0 mmol) in dry THF (50 ml). The obtained mixture was heated under reflux for 4 h and then cooled to room temperature. EtOAc (200 ml), water (40 ml), and a 2 N aqueous solution of NaOH (10 ml) were added. The obtained mineral precipitate was filtered through a pad of kiselguhr, the filtrate evaporated in vacuo and water (50 ml) added to the residue. The aqueous layer was extracted with CH2CI2 (3 x 50 ml) and the organic extracts combined and dried over Na2SO4, filtered and evaporated in vacuo to give the product as a colourless oil (1.75 g, 85.6 percent). H-NMR (200 MHz, CDCl3) : 8 7.40-7. 26 (m, 5 H), 3.53-3. 46 (m, 4 H), 2.94 (d, 2 H), 2.61 (br s, 1 H), 2.00 (t, 2 H), 1.75 (d, 2 H), 1.48-1. 26 (m, 3 H)5L reaction flask to dry slowly purged with nitrogen, will 233.3g1-benzyl-4-piperidine carboxylic acid methyl ester (1mol) and 240ml of toluene into a reactor, with stirring, cooled until the internal temperature at about -5 . The resulting red aluminum - morpholine complex (approximately 2.6mol) was dropped to control the reaction temperature between -5 ~ 0 . 3h addition was complete, the reaction was continued insulation 2h. Was added slowly prepared 4N sodium hydroxide solution (containing 360gNaOH), control the internal temperature not higher than 20 , the addition was completed, stirring was stopped, the organic layer was washed with water (1500ml / times, 4 times), the organic layer was concentrated at 75 concentrated under reduced pressure until no solvent was evaporated to give 5L reaction flask to dry slowly purged with nitrogen, will 233.3g1-benzyl-4-piperidine carboxylic acid methyl ester (1mol) and 240ml of toluene into a reactor, with stirring, cooled until the internal temperature at about -5 . The resulting red aluminum - morpholine complex (approximately 2.6mol) was dropped to control the reaction temperature between -5 ~ 0 . 3h addition was complete, the reaction was continued insulation 2h. Was added slowly prepared 4N sodium hydroxide solution (containing 360gNaOH), control the internal temperature not higher than 20 , the addition was completed, stirring was stopped, the organic layer was washed with water (1500ml / times, 4 times), the organic layer was concentrated at 75 concentrated under reduced pressure until no solvent was evaporated to give Description 7 (intermediate for Example 15) (1-Benzyl-4-piperidyl)methanol Ethyl isonipectoate was intially alkylated with benzyl bromide and the product reduced with lithium aluminium hydride using the method of Description 6, to afford the title compound (D7) as a colourless oil (100percent). 1 H NMR (CDCl3); delta: 7.20-7.35(m, 5H), 3.52(s, 2H), 3.48(d, 2H), 2.86-3.00(m, 2H), 1.20-2.05(m, 8H).Description 7 (Intermediate for Example 15) (1-Benzyl-4-piperidyl)Methanol Ethyl isonipectoate was intially alkylated with benzyl bromide and the product reduced with lithium aluminium hydride using the method of Description 6, to afford the title compound (D7) as a colourless oil (100percent).

Molecular Weight:205.30
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:205.146664230
Monoisotopic Mass:205.146664230
Topological Polar Surface Area:23.5
Heavy Atom Count:15
Complexity:169
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes