2-(3-BUTYNYLOXY)TETRAHYDRO-2H-PYRAN

A mixture of 4-dihydro-2H-pyridine (293.2 g 3.5 mol) and concentrated HCl (1. 1 mL) was cooled to 5 °C. While continuing to cool externally, 3-BUTYN-1-OL (231.5 g, 3.3 mol) was added over a period of 30 min allowing the temperature to reach 50 °C. Reaction was held with mixing at room temperature for 2.5 hr before it was diluted with MTBE (1.0 L). The resulting mixture was washed with saturated sodium bicarbonate (2X150 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure to afford 500 g (98percent crude yield) of product; GC areapercent of 96percent.2-But-3-ynyloxy-tetrahydro-pyran (2)A solution of 3-butyn-l-ol 1 (1.0Og, 14.3 mmol) and PPTS (0.72g, 2.9 mmol) in CHPyridinium p-toluene sulfonate (10.43 g, 41.5 mmol) was added to a solution of 3-butyn-1-ol (30.0 mL, 396 mmol) and 3, 4-dihydro-2H-pyran (37.9 mL, 415 mmol) in CH2Cl2 (150 mL), and the whole was stirred at 0 C for 2 h and then at room temperature for a further 1.5 h. The reaction was quenched with saturated aqueous NaHCO3 solution (150 mL) and the aqueous layer extracted with CH2Cl2 (150 mL). The combined organic extracts were dried (MgSO4), and the solvent removed in vacuo. The residue was purified by distillation (bp 70–102C, 24 mm Hg; 96–104 C, 24 mm Hg) to yield the title compound as a pale yellow oil (51.26 g, 84percent); Rf 0.42 [petroleum ether (40–60C)–EtOAc, 5:1]. IR (neat, max, cm-1): 3291, 2941, 2870. 1H NMR (400 MHz, CDCl3, , ppm, J/Hz): 4.54 (1H, t, J = 3.5, H-2), 3.78 (1H, ddd, J = 11.7, 8.4, 3.1, H-6), 3.72 (1H, td, J = 9.7, 7.0, H-6), 3.46 (1H, td, J = 9.7, 7.0, H-1), 3.43–3.38 (1H, m, H-1), 2.38 (2H, td, J = 7.0, 2.6, H-2), 1.89 (1H, t, J = 2.6, H-4), 1.78–1.69 (1H, m, H-3), 1.62 (1H, dt, J = 11.6, 3.5, H-3), 1.54–1.38 (4H, m, H-4, 5). 13C NMR (100 MHz, CDCl3, , ppm): 98.6 (CH), 81.3 (C), 69.2 (CH), 65.4 (CH2), 62.0 (CH2), 30.4 (CH2), 25.3 (CH2), 19.8 (CH2), 19.3 (CH2). LC-MS (ES+) m/z 155 [M + H]+, [M]+ C9H14O2. Spectral data were consistent with literature values [18].A solution of 3-butyn-1-ol (50 g, 1 equiv, 713 mmol), p-toluenesulfonic acid monohydrate (1.36 g, 0.01 equiv, 7.13 mmol), and dihydropyran (71.7 mL, 1.10 equiv, 785 mmol) in dichloromethane (500 mL) is stirred at 25° C. for 24 hours. To but-3-yn-1-ol (40.0 g, 570.0 mmol) and 3, 4-dihydro-2H-pyran (48.0 g, 570.0 mmol) in anhydrous dichloromethane (350 mL) was added pyridium p-toluenesulfonate (0.45 g, 1.80 mmol). The mixture was stirred at room temperature for 16 hours. Solvent was evaporated, and the residue was purified by vacuum distillation to give 2-but-3-ynyloxy-tetrahydro-pyran as a light yellow liquid. Yield: 60.0 g (68percent)To but-3-yn-1-ol (40.0 g, 570.0 mmol) and 3, 4-dihydro-2H-pyran (48.0 g, 570.0 mmol) in anhydrous dichloromethane (350 mL) was added pyridium p-toluenesulfonate (0.45 g, 1.80 mmol). 10.0 g (0.14 mol) of a compound represented by the formula (I-9a) and 1.79 g (7.1 mmol) of pyridinium p-toluenesulfonate were added to a flask and dissolved in 50 mL of dichloromethane. While ice-cooling, a dichloromethane solution of 15.6 g (0.19 mol) of 3, 4-dihydro-2H-pyran was added dropwise. After stirring at room temperature for 6 hours, it was washed with saturated aqueous sodium bicarbonate solution and brine. By distilling off the solvent, the compound represented by the formula (I-9b) 21.8 g (0.14 mol) was obtained.

Molecular Weight:154.21
XLogP3:1.5
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:154.099379685
Monoisotopic Mass:154.099379685
Topological Polar Surface Area:18.5
Heavy Atom Count:11
Complexity:145
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes