3,4-dihydro-2H-pyran-2-ylmethanol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Tert-butyl hydroperoxide (5.5M, 4.73 mmoles) was added to a mixture of vanadyl acetoacetonate (0.058 g, 0.22 mmoles) and hydroxymethyldihydro-pyran (0.5 g, 4.38 mmoles) in 16.2 ml of toluene at 85° C. After stirring for 5 minutes, TLC showed the reaction to be complete. The mixture was diluted with ethyl acetate and washed with 1 M hydrochloric acid followed by a wash with a saturated sodium bicarbonate solution. The ethyl acetate layer was dried over sodium sulfate, filtered and concentrated in vacuo to yield a light yellow oil (0.4 g, 70%). 1H NMR (D6 acetone, 400 MHz) δ 3.21 (bs, 1H), 3.36-3.42 (m, 2H), 3.48 (dd, J=6.64 Hz and 12.04 Hz, 1H), 3.6 (dd, J=5.61 Hz and 12.04 Hz, 1H), 3.74 (d, J=13.07 Hz, 1H), 3.87 (dd, J=5.6 Hz and 6.64 Hz, 1H), 4.02 (d, J=13.07 Hz, 1H). the reaction washed with 1 M hydrochloric acid a wash with a saturated sodium bicarbonate solution The ethyl acetate layer was dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of (±)-3,4-dihydro-2H-pyran-2-methanol (514 g, 4.51 mol, 1 eq) and acetic anhydride (621 g, 6.09 mol, 1.35 eq) was cooled to 0° C. To the resultant mixture was added pyridine (35.6 g, 0.45 mol, 0.1 eq) and the resultant reaction mixture was allowed to warm to room temperature with stirring. The resultant reaction mixture was allowed to stir for an additional 8 hours after reaching room temperature and was shown to be complete by thin-layer chromatography (2:1 hexanes:ethyl acetate, 12 staining). The reaction mixture was concentrated in vacuo at 35° C. and the resultant residue was diluted using ethyl acetate (2 L). The resultant mixture was transferred to a separatory funnel and sequentially washed with deionized water (3×1 L), saturated aqueous NaHCO3 (2×10 L), and brine (1.0 L). The organic layer was dried over sodium sulfate and concentrated in vacuo at 35° C. to provide (±)-3,4-dihydro-2H-pyran-2-yl-methyl acetate as a clear liquid (605.9 g, 86% yield). 1H NMR (300 MHz, CDCl3) δ 1.6-2.2 (m, 4 H), 2.1 (s, 3 H), 4.2 (m, 3 H), 4.8 (m, 1 H), 6.4 (m, 1 H). the resultant reaction mixture to warm to room temperature The resultant reaction mixture to stir for an additional 8 hours after reaching room temperature The reaction mixture was concentrated in vacuo at 35° C. the resultant residue was diluted The resultant mixture was transferred to a separatory funnel sequentially washed with deionized water (3×1 L), saturated aqueous NaHCO3 (2×10 L), and brine (1.0 L) The organic layer was dried over sodium sulfate concentrated in vacuo at 35° C.

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of (±)-3,4-dihydro-2H-pyran-2-methanol (514 g, 4.51 mol, 1 eq) and acetic anhydride (621 g, 6.09 mol, 1.35 eq) was cooled to 0° C. To the resultant mixture was added pyridine (35.6 g, 0.45 mol, 0.1 eq) and the resultant reaction mixture was allowed to warm to room temperature with stirring. The resultant reaction mixture was allowed to stir for an additional 8 hours after reaching room temperature and was shown to be complete by thin-layer chromatography (2:1 hexanes:ethyl acetate, 12 staining). The reaction mixture was concentrated in vacuo at 35° C. and the resultant residue was diluted using ethyl acetate (2 L). The resultant mixture was transferred to a separatory funnel and sequentially washed with deionized water (3×1 L), saturated aqueous NaHCO3 (2×10 L), and brine (1.0 L). The organic layer was dried over sodium sulfate and concentrated in vacuo at 35° C. to provide (±)-3,4-dihydro-2H-pyran-2-yl-methyl acetate as a clear liquid (605.9 g, 86% yield). 1H NMR (300 MHz, CDCl3) δ 1.6-2.2 (m, 4 H), 2.1 (s, 3 H), 4.2 (m, 3 H), 4.8 (m, 1 H), 6.4 (m, 1 H). the resultant reaction mixture to warm to room temperature The resultant reaction mixture to stir for an additional 8 hours after reaching room temperature The reaction mixture was concentrated in vacuo at 35° C. the resultant residue was diluted The resultant mixture was transferred to a separatory funnel sequentially washed with deionized water (3×1 L), saturated aqueous NaHCO3 (2×10 L), and brine (1.0 L) The organic layer was dried over sodium sulfate concentrated in vacuo at 35° C.

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of (±)-3,4-dihydro-2H-pyran-2-methanol (514 g, 4.51 mol, 1 eq) and acetic anhydride (621 g, 6.09 mol, 1.35 eq) was cooled to 0° C. To the resultant mixture was added pyridine (35.6 g, 0.45 mol, 0.1 eq) and the resultant reaction mixture was allowed to warm to room temperature with stirring. The resultant reaction mixture was allowed to stir for an additional 8 hours after reaching room temperature and was shown to be complete by thin-layer chromatography (2:1 hexanes:ethyl acetate, I2 staining). The reaction mixture was concentrated in vacuo at 35° C. and the resultant residue was diluted using ethyl acetate (2 L). The resultant mixture was transferred to a separatory funnel and sequentially washed with deionized water (3×1 L), saturated aqueous NaHCO3 (2×10 L), and brine (1.0 L). The organic layer was dried over sodium sulfate and concentrated in vacuo at 35° C. to provide (±)-3,4-dihydro-2H-pyran-2-yl-methyl acetate as a clear liquid (605.9 g, 86% yield). 1H NMR (300 MHz, CDCl3) δ 1.6-2.2 (m, 4H), 2.1 (s, 3H), 4.2 (m, 3H), 4.8 (m, 1H), 6.4 (m, 1H). the resultant reaction mixture to warm to room temperature The resultant reaction mixture to stir for an additional 8 hours after reaching room temperature The reaction mixture was concentrated in vacuo at 35° C. the resultant residue was diluted The resultant mixture was transferred to a separatory funnel sequentially washed with deionized water (3×1 L), saturated aqueous NaHCO3 (2×10 L), and brine (1.0 L) The organic layer was dried over sodium sulfate concentrated in vacuo at 35° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Whilst cooling a solution of 14.2 g of 2-hydroxymethyl-3,4-dihydro-2H-pyran in 120 ml of pyridine on an ice-water bath at 0°-5° C., 28.4 g of crystals of tosyl chloride were added and the mixture was then stirred at room temperature overnight. The salt which precipitated with the aid of a Celite (Trademark) filter aid was separated by filtration and the filtrate was concentrated under reduced pressure. Water was added to the residue and the resulting mixture was extracted with diethyl ether. The ethereal extract was washed with a saturated aqueous solution of sodium bicarbonate and then with aqueous sodium chloride, after which the solvent was evaporated off under reduced pressure. The residue was purified by column chromatography through silica gel eluted with a 7:1 by volume mixture of hexane and ethyl acetate, to give 31.5 g of the title compound, in the form of colourless crystals melting at 47°-48° C. The salt which precipitated with the aid of a Celite (Trademark) filter aid was separated by filtration the filtrate was concentrated under reduced pressure Water was added to the residue the resulting mixture was extracted with diethyl ether The ethereal extract was washed with a saturated aqueous solution of sodium bicarbonate with aqueous sodium chloride, after which the solvent was evaporated off under reduced pressure The residue was purified by column chromatography through silica gel eluted with a 7:1 by volume mixture of hexane and ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9.77 g of benzoyl chloride were slowly added dropwise to a solution of 7.20 g of 2-hydroxymethyl-3,4-dihydro-2H-pyran in 14 ml of dry pyridine, whilst cooling the solution on an ice-water bath. When the addition was complete, the mixture was stirred at room temperature for 2 hours and then poured into an aqueous solution of sodium bicarbonate. The mixture was extracted with diethyl ether and the ethereal extract was washed with aqueous sodium chloride and dried over anhydrous sodium sulphate. The solvent was then evaporated off under reduced pressure and the residue was purified by distillation under reduced pressure, to give the title compound boiling at 112°-113° C./10 mmHG. whilst cooling the solution on an ice-water bath When the addition The mixture was extracted with diethyl ether the ethereal extract was washed with aqueous sodium chloride dried over anhydrous sodium sulphate The solvent was then evaporated off under reduced pressure the residue was purified by distillation under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Tert-butyl hydroperoxide (5.5M, 4.73 mmoles) was added to a mixture of vanadyl acetoacetonate (0.058 g, 0.22 mmoles) and hydroxymethyldihydro-pyran (0.5 g, 4.38 mmoles) in 16.2 ml of toluene at 85° C. After stirring for 5 minutes, TLC showed the reaction to be complete. The mixture was diluted with ethyl acetate and washed with 1 M hydrochloric acid followed by a wash with a saturated sodium bicarbonate solution. The ethyl acetate layer was dried over sodium sulfate, filtered and concentrated in vacuo to yield a light yellow oil (0.4 g, 70%). 1H NMR (D6 acetone, 400 MHz) δ 3.21 (bs, 1H), 3.36-3.42 (m, 2H), 3.48 (dd, J=6.64 Hz and 12.04 Hz, 1H), 3.6 (dd, J=5.61 Hz and 12.04 Hz, 1H), 3.74 (d, J=13.07 Hz, 1H), 3.87 (dd, J=5.6 Hz and 6.64 Hz, 1H), 4.02 (d, J=13.07 Hz, 1H). the reaction washed with 1 M hydrochloric acid a wash with a saturated sodium bicarbonate solution The ethyl acetate layer was dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of (±)-3,4-dihydro-2H-pyran-2-methanol (514 g, 4.51 mol, 1 eq) and acetic anhydride (621 g, 6.09 mol, 1.35 eq) was cooled to 0° C. To the resultant mixture was added pyridine (35.6 g, 0.45 mol, 0.1 eq) and the resultant reaction mixture was allowed to warm to room temperature with stirring. The resultant reaction mixture was allowed to stir for an additional 8 hours after reaching room temperature and was shown to be complete by thin-layer chromatography (2:1 hexanes:ethyl acetate, 12 staining). The reaction mixture was concentrated in vacuo at 35° C. and the resultant residue was diluted using ethyl acetate (2 L). The resultant mixture was transferred to a separatory funnel and sequentially washed with deionized water (3×1 L), saturated aqueous NaHCO3 (2×10 L), and brine (1.0 L). The organic layer was dried over sodium sulfate and concentrated in vacuo at 35° C. to provide (±)-3,4-dihydro-2H-pyran-2-yl-methyl acetate as a clear liquid (605.9 g, 86% yield). 1H NMR (300 MHz, CDCl3) δ 1.6-2.2 (m, 4 H), 2.1 (s, 3 H), 4.2 (m, 3 H), 4.8 (m, 1 H), 6.4 (m, 1 H). the resultant reaction mixture to warm to room temperature The resultant reaction mixture to stir for an additional 8 hours after reaching room temperature The reaction mixture was concentrated in vacuo at 35° C. the resultant residue was diluted The resultant mixture was transferred to a separatory funnel sequentially washed with deionized water (3×1 L), saturated aqueous NaHCO3 (2×10 L), and brine (1.0 L) The organic layer was dried over sodium sulfate concentrated in vacuo at 35° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3,4-Dihydro-2H-pyran-2-ylmethanol (5.0 g) was dissolved in tetrahydrofuran (100 ml). 55% Sodium hydride (2.3 g) and benzyl bromide (8.2 g) were added under ice-cooling, followed by stirring for 17 hours. A saturated aqueous ammonium chloride solution was added, followed by extraction with ethyl acetate and washing with brine. The organic layer was dried over anhydrous sodium sulfate and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (developed with ethyl acetate-hexane) to give the title compound (8.5 g) as a pale yellow oil. cooling followed by extraction with ethyl acetate washing with brine The organic layer was dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (developed with ethyl acetate-hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a dried round bottomed flask under argon atmosphere, 60% sodium hydride (240 mg, 6.0 mmol) was rinsed three times with anhydrous n-pentane. A solution of 2-hydroxymethyl-3,4-dihydro-2H-pyran (570.8 mg, 5 mmol) in tetrahydrofuran (10 ml) was cooled at 0° C. and then added to the NaH. The reaction mixture was stirred at 0° C. until hydrogen evolution ended. A solution of ethyl bromoacetate (1253 mg, 7.5 mmol) in tetrahydrofuran (6 ml) was added to the reaction mixture and the stirring was continued at room temperature until disappearance of the starting alcohol (TLC analysis). After cooling, H2O was added, and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (AcOEt:hexane=1:12) on silica gel (230-400 mesh), affording 626 mg (yield 57%) of ethyl (3,4-dihydro-2H-pyran-2-ylmethoxy)acetate as a colorless oil; 1H NMR (401 MHz, DMSO-d6) δ ppm 1.18-1.23 (m, 3H) 3.55-3.59 (m, 2H) 3.93 (m, J=10.08, 5.11, 5.11, 2.38 Hz, 1H) 4.13 (q, J=7.07 Hz, 2H) 4.14 (s, 2H) 4.67 (dddd, J=6.14, 4.83, 2.56, 1.34 Hz, 1H) 6.36 (dt, J=6.13, 1.75 Hz, 1H). After cooling the solvent was evaporated under reduced pressure The residue was purified by flash column chromatography (AcOEt:hexane=1:12) on silica gel (230-400 mesh)