2-dec-9-ynoxyoxane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7.4 g of compound IV, 1.0 g lithium amide, and 50 ml of dry, purified dioxane was stirred and refluxed 3.5 hours under nitrogen, cooled, 4.5 g of n-butyl bromide was added dropwise and the refluxing and stirring continued for 20 hours more. The mixture was chilled in an icebath, diluted with 60 ml of water and the layers separated. The aqueous layer was extracted three times with ether, the combined organic phase was washed three times with saturated NaCl solution, the solvents were evaporated and the residue distilled to give 3.2 g (36%) of compound V which boiled at 120°-123° (0.03 mm), ND25 1.4634. of dry purified dioxane refluxed 3.5 hours under nitrogen cooled 4.5 g of n-butyl bromide was added dropwise the refluxing and stirring The mixture was chilled in an icebath diluted with 60 ml of water the layers separated The aqueous layer was extracted three times with ether the combined organic phase was washed three times with saturated NaCl solution the solvents were evaporated the residue distilled

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flame-dried round-bottomed flask was charged with 9-decyn-1-ol tetrahydropyranyl ether (1 equiv, 31.7 mmol, 7.55 g) and THF (40 mL), and cooled to −78° C. n-BuLi (1.1 equiv, 34.9 mmol, 21.8 mL of a nominally 1.6 M solution in hexanes) were added dropwise over 5 min. The reaction was stirred for 30 min at −78° C. and then added to a solution of methyl chloroformate (1.5 eq, 47.6 mmol, 4.50 g, 3.7 mL) in THF (20 mL) dropwise via cannula. The reaction was stirred for 30 min at −78° C., then warmed to rt over 1 h and quenched dropwise with H2O (40 mL). The layers were separated and the aqueous layer was extracted with Et2O (2×25 mL). The combined organic layers were dried with Na2SO4, evaporated in vacuo, and purified by flash column chromatography (step gradient, 5% EtOAc/Hex to 10% EtOAc/Hex) to afford Methyl-11-[(tetrahydro-2H-pyran-2-yl)oxy]-undecynoate (8.50 g, 28.7 mmol, 90%). TLC Rf=0.33 (10% EtOAc/Hex) 1HNMR (600 MHz): δ 4.55-4.61 (1H), 3.84-3.91 (m, 1H), 3.70-3.78 (m plus ovlp. s, 4H), 3.47-3.54 (m, 1H), 3.39 (dt, 1H, J1=9.6 Hz, J2=6.7 Hz), 2.33 (t, 2H, J=7.1 Hz), 1.80-1.89 (1H), 1.68-1.76 (1H), 1.50-1.63 (8H), 1.28-1.44 (8H); 13CNMR (150 MHz): δ 154.3, 98.9, 89.9, 72.9, 67.6, 62.3, 52.5, 30.8, 29.7, 29.2, 28.9, 28.7, 27.5, 26.2, 25.5, 19.7, 18.6; FTIR: 2932, 2856, 2236, 1714, 1434, 1249, 1075, 1023, 752 cm−1; HRMS-ESI: calc. for C17H28NaO4 (M+Na)+: 319.1885. found: 319.1887. were added dropwise over 5 min The reaction was stirred for 30 min at −78° C. warmed to rt over 1 h quenched dropwise with H2O (40 mL) The layers were separated the aqueous layer was extracted with Et2O (2×25 mL) The combined organic layers were dried with Na2SO4 evaporated in vacuo purified by flash column chromatography (step gradient, 5% EtOAc/Hex to 10% EtOAc/Hex)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a flame-dried round-bottomed flask was added 9-decyn-1-ol (1 equiv, 32.4 mmol, 5.00 g), dihydropyran (1.5 equiv, 48.6 mmol, 4.09 g, 4.5 mL), CH2Cl2 (50 mL), and PPTS (0.1 equiv, 3.24 mmol, 800 mg). The reaction was stirred for 16 h at rt and quenched with sat. aq. NaHCO3 (40 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (2×20 mL). The combined organic layers were washed with H2O (30 mL), dried with Na2SO4, concentrated in vacuo, and purified by flash column chromatography (5% EtOAc/Hex) to afford 9-Decyn-1-ol tetrahydropyranyl ether (7.55 g, 31.7 mmol, 98%). TLC Rf=0.30 (5% EtOAc/Hex); 1HNMR (600 MHz): δ 4.55-4.62 (1H), 3.83-3.91 (m, 1H), 3.70-3.78 (m, 1H), 3.48-3.55 (m, 1H), 3.36-3.43 (m, 1H), 2.19 (td, 2H, J1=7.1 Hz, J2=2.6 Hz), 1.95 (t, 1H, J=2.6), 1.80-1.89 (1H), 1.69-1.76 (1H), 1.50-1.63 (8H), 1.28-1.44 (8H); 13CNMR (150 MHz): δ 98.8, 84.7, 68.1, 67.6, 62.3, 30.8, 29.7, 29.3, 29.0, 28.7, 28.5, 26.2, 25.5, 19.7, 18.4. quenched with sat. aq. NaHCO3 (40 mL) The layers were separated the aqueous layer was extracted with CH2Cl2 (2×20 mL) The combined organic layers were washed with H2O (30 mL) dried with Na2SO4 concentrated in vacuo purified by flash column chromatography (5% EtOAc/Hex)