5-BENZYLOXY-1-PENTANOL

To a stirred suspension of 60percent dispersion of NaH in mineral oil (2.30 g, 57.69 mmol) was added a solution of 1, 5-pentanediol 9 (5.0 g, 48.07 mmol) in dry DMF (150 mL) slowly over a period of 15 min at 0 °C. Then reaction mixture was stirred at room temperature for 1 h followed by addition of benzyl bromide (5.75 mL, 48.07 mmol) over 15 min and the stirred for additional 2 h at the same temperature. The reaction mixture was quenched with ice cold water. The crude mixture was extracted with ethyl acetate (2 x 30 mL) and the organic layer was washed with brine (3 times) and dried over anhydrous NaA flame dried, 500-mL three-necked, round-bottomed flask equipped with a magnetic stirring bar was charged withNaH (8.12 g, 60percent in mineral oil, 203 mmol) and THF (200 mL). To the suspension was added dropwise1, 5-pentanediol (16) (42.0 mL, 400 mmol) at 0 °C. The reaction mixture was heated at reflux, and DMF (10 mL) andbenzyl bromide (24.0 mL, 202 mmol) were added dropwise to the mixture at the same temperature. After stirring for 3 h, the resulting suspension was diluted with H2O and the mixture was extracted with EtOAc three times. The combinedorganic extracts were washed with H2O and brine, dried over anhydrous Na2SO4, filtered, and concentrated underreduced pressure. The residue was purified by flash column chromatography on silica gel (hexanes/EtOAc = 7:3 to 4:6)to give alcohol s-1 (28.7 g, 148 mmol, 73percent) as a colorless oil. Its spectral data were identical with those reported.11 , 5-Pentandiol (3.430 g, 3.45 mL, 0.033 mol, 4 eq.) was added dropwise to a suspension of NaH (670 mg, 0, 016 mol, 2 eq) in DMF (14 mL) at 0°C. A catalytic amount of Nal was added, followed by benzylbromide (1.360 g, 0, 95 mL, 0.008 mol, 1 eq.).The mixture was stirred at r.t. overnight.The reaction was quenched with NH4CI aq. sat. and then extracted with ethyl acetate (x3). Organic layers were collected and evaporated under reduced pressure. The crude was purified by flash chromatography eluting from 40percent to 90percent of ethyl acetate in heptane to give the desired product (1.08 g, yield: 70percent)A solution of pentane-1, 5-diol (21 mL, 200 mmol) in THF (400 mL) was added drop wise to a stirred suspension of oil free sodium hydride (4.8 g, ∼55percent in oil, 200 mmol) in THF (100 mL) under argon atmosphere. The reaction mixture was heated under reflux for 4 h, cooled to room temperature and benzyl bromide (23.7 mL, 200 mmol) was drop wise added to it. The reaction mixture was heated under reflux overnight, cooled to room temperature and concentrated under reduced pressure. The residue was diluted with water and extracted with ethyl acetate. The organic extract was concentrated under reduced pressure and purified by fractional distillation to give 5-(benzyloxy)pentane-1-ol (25.2 g, 65percent); bp 140–150 °C (bath) (0.4 mbar) as a colorless liquid. p-Toluenesulphonyl chloride (24.8 g, 130 mmol) was added to a stirred solution of 5-(benzyloxy)pentane-1-ol (25.2 g, 130 mmol) in dry pyridine (30 mL) at 0 °C. The reaction mixture was left standing at 4 °C overnight. The reaction mixture was allowed to attain to room temperature, diluted with water and extracted with 15percent ethyl acetate in hexanes. The organic extract was concentrated under reduced pressure to give 5-(benzyloxy)pentyl-1-(4-methyl)benzenesulfonate (42.5 g, 94percent) as a colorless gum. Sodium bromide (13 g, 126 mmol) was added to the stirred solution of 5-(benzyloxy)pentyl-1-(4-methyl)benzenesulfonate (42.5 g, 122 mmol) in DMF (300 mL) and the reaction mixture was heated at 45 °C for 5 h. The reaction mixture was diluted with water, and extracted with 10percent ethyl acetate in hexanes. The organic extract was concentrated to give bromide 2 (31.3 g, 99percent) as a colorless liquid. IR (film): υ 3063, 3029, 2937, 2859, 1646, 1495, 1454, 1362, 1245, 1203, 1103, 1027, 735, 697 cmAt 0° C., 1, 5-pentanediol (40 g, 0.39 mol) was added into 200 ml dry THF. Sodium hydride (4.6 g, 0.19 mol) was added in batches within 30 min. The temperature returned to the room temperature for a 2 h reaction. Benzyl bromide (33 g, 0.19 mol) was dissolved in 20 ml THF, which was dropped into the aforementioned system at 0° C. followed by reflux for 4 h. After the complete of the reaction, the reaction was quenched with cold water. The organic phase was extracted with diethyl ether. After drying the organic phase with anhydrous sodium sulfate, it was filtered, then subject to rotatory evaporation to remove the solvent, followed by reduced pressure distillation to obtain 23.1 g of colorless oily liquid 3 with a yield of 62percent. Into a 1000 mL round-bottom flask, was placed pentane-1, 5-diol (30 g, 288.05 mmol, 1.00 equiv), tetrahydrofuran (500 mL). This was followed by the addition of sodium hydride (13.8 g, 575.00 mmol, 2.00 equiv) in several batches. The mixture was stirred for 1 h at 25 oC. To this was added BnBr (58 g, 339.12 mmol, 1.20 equiv) dropwise with stirring. The resulting solution was stirred overnight at 25 oC. The reaction was then quenched by the addition of 50 mL of water. The resulting solution was extracted with 3x500 mL of ethyl acetate and the organic layers were combined and dried over anhydrous sodium sulfate. The solids were filtered out. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column eluted with ethyl acetate/petroleum ether (1:5). This resulted in 28 g (50percent) of 5-(benzyloxy)pentan-1-ol as colorless oil. (1892) LC-MS m/z: (ES+) [M+H] + = 195; Retention time: 1.01 min; (1893) 1H NMR (300 MHz, CDCl3, 25 oC): 7.35 (s, 5H), 4.52 (s, 2H), 3.65 (t, 2H), 3.51 (t, 2H), 1.69- 1.40 (m, 6H).

Molecular Weight:194.27
XLogP3:2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:7
Exact Mass:194.130679813
Monoisotopic Mass:194.130679813
Topological Polar Surface Area:29.5
Heavy Atom Count:14
Complexity:120
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes