2-pent-4-ynoxyoxane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 3,4-Dihydro-2H-pyran (5.0 g) was added dropwise to an ice cooled mixture of 4-pentyn-1-ol (5.0 g) and 4-methylbenzenesulfonic acid (0.512 g). The resultant mixture was stirred at room temperature for 4 hours. Solid sodium bicarbonate (1.0 g) was added and the mixture was stirred for 10 minutes, then filtered and washed with diethyl ether. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-100% to give 2-(pent-4-ynyloxy)tetrahydropyran (7.72 g) as a clear oil. cooled filtered washed with diethyl ether The filtrate was concentrated in vacuo the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-100%

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

Procedure: 3,4-Dihydro-2H-pyran (5.0 g) was added dropwise to an ice cooled mixture of 4-pentyn-1-ol (5.0 g) and 4-methylbenzenesulfonic acid (0.512 g). The resultant mixture was stirred at room temperature for 4 hours. Solid sodium bicarbonate (1.0 g) was added and the mixture was stirred for 10 minutes, then filtered and washed with diethyl ether. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-100% to give 2-(pent-4-ynyloxy)tetrahydropyran (7.72 g) as a clear oil. cooled filtered washed with diethyl ether The filtrate was concentrated in vacuo the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-100%

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of n-butyllithium (2.5M in hexanes, 22 mL) was added dropwise to a solution of 2-(pent-4-ynyloxy)tetrahydropyran (Intermediate 25, 7.70 g) in THF (60 mL), at −60° C. The mixture was stirred and allowed to warm to 15° C. over 1 hour. It was then re-cooled to −60° C. and a solution of tributyl tin chloride (16.4 g) in THF (50 mL) was added dropwise over 30 minutes. The mixture was stirred and allowed to warm to 20° C. over 1 hour. 1M aqueous sodium hydroxide (4 mL) was cautiously added and the resultant mixture was filtered through Celite, and washed with ethyl acetate. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-100% to give tributyl-[5-(tetrahydropyran-2-yloxy)-pent-1-ynyl]-stannane (5.44 g). It was then re-cooled to −60° C. The mixture was stirred to warm to 20° C. over 1 hour the resultant mixture was filtered through Celite washed with ethyl acetate The filtrate was concentrated in vacuo the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-100%

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

Procedure: 1-(Tetrahydopyran-2-yloxy)-4-pentyne (1) (0.66 g, 3.90 mmol) was metallated with n-butyllithium solution (2.5M) in hexane (1.87 ml, 1.2 eq.). Addition of a solution of n-pentyl bromide (0.725 ml, 1.5 eq.) in DMPU (2 ml) produced 0.54 g (58% yield) of the title compound (15). 1H NMR (200 MHz) δ: 4.60 (m, 1H, CH-2'), 3.65 (m, 4H, CH2 -1, 6'), 2.26 (tt, J=7.0, 7.0, 2.0, 2.0 Hz, 2H, CH2 -3), 2.13 (tt, J=7.0, 7.0, 2.5, 2.5 Hz, 2H, CH2 -6), 1.77 (tt, J=6.8, 6.8, 7.07 7.0 Hz, 2H, CH2 -2), 1.33 (m, 6H, CH2 -7, 8, 9), 1.52 (m, 6H, CH2 -3', 4', 5'), 0.89 (t, J=7.0 Hz, 3H, CH3). MS [FAB, m/z(%)] 237 (M+ -1), 85 (100). IR (CCl4, cm-1) 2229, 1322, 1331, 1201, 1138, 1121, 1034.

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

Procedure: Hydrazine hydrate and hydrogen peroxide (30 wt. % solution in water) were purchased from Mallinckrodt (Chesterfield, Mo.) and Fisher Chemical Co. (Fair Lawn, N.J.), respectively. Butyllithium (1.6M and 2.5M solutions in hexane), 2-(3-butynyloxy)tetrahydro-2H-pyran (1-(tetrahydopyran-2-yloxy)-3-butyne), lithium tetrahydridoaluminate, borane-methylsulfide complex, Cu(I)Br.Me2S complex, and p-toluenesulfonyl chloride from Aldrich Chemical Co. (Milwaukee, Wis.), and bromine and triphenylphosphine from Fluka Chemical Co. (Ronkonkoma, N.Y.), were used as purchased. 1-(Tetrahydopyran-2-yloxy)-4-pentyne was prepared from the corresponding alcohol using the methods described in Robertson, "Adducts of tert-alcohols containing an ethynyl group with dihydropyran. Potentially useful intermediates," J. Org. Chem. 25:931-932 (1960), the disclosure of which is hereby incorporated by reference. Column chromatography was run on silica gel (Merck, H 60), and reactions were monitored by TLC on Baker-flex Silica gel IB2-F plates (J. T. Baker). Silver nitrate column chromatography was done on silica gel impregnated with AgNO3 (20% of AgNO3 on silica gel Merck H 60).

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

Procedure: 1-(Tetrahydopyran-2-yloxy)-4-pentyne (1) (0.66 g, 3.90 mmol) was metallated with n-butyllithium solution (2.5M) in hexane (1.87 ml, 1.2 eq.). Addition of a solution of n-pentyl bromide (0.725 ml, 1.5 eq.) in DMPU (2 ml) produced 0.54 g (58% yield) of the title compound (15). 1H NMR (200 MHz) δ: 4.60 (m, 1H, CH-2'), 3.65 (m, 4H, CH2 -1, 6'), 2.26 (tt, J=7.0, 7.0, 2.0, 2.0 Hz, 2H, CH2 -3), 2.13 (tt, J=7.0, 7.0, 2.5, 2.5 Hz, 2H, CH2 -6), 1.77 (tt, J=6.8, 6.8, 7.07 7.0 Hz, 2H, CH2 -2), 1.33 (m, 6H, CH2 -7, 8, 9), 1.52 (m, 6H, CH2 -3', 4', 5'), 0.89 (t, J=7.0 Hz, 3H, CH3). MS [FAB, m/z(%)] 237 (M+ -1), 85 (100). IR (CCl4, cm-1) 2229, 1322, 1331, 1201, 1138, 1121, 1034.

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

Procedure: Hydrazine hydrate and hydrogen peroxide (30 wt. % solution in water) were purchased from Mallinckrodt (Chesterfield, Mo.) and Fisher Chemical Co. (Fair Lawn, N.J.), respectively. Butyllithium (1.6M and 2.5M solutions in hexane), 2-(3-butynyloxy)tetrahydro-2H-pyran (1-(tetrahydopyran-2-yloxy)-3-butyne), lithium tetrahydridoaluminate, borane-methylsulfide complex, Cu(I)Br.Me2S complex, and p-toluenesulfonyl chloride from Aldrich Chemical Co. (Milwaukee, Wis.), and bromine and triphenylphosphine from Fluka Chemical Co. (Ronkonkoma, N.Y.), were used as purchased. 1-(Tetrahydopyran-2-yloxy)-4-pentyne was prepared from the corresponding alcohol using the methods described in Robertson, "Adducts of tert-alcohols containing an ethynyl group with dihydropyran. Potentially useful intermediates," J. Org. Chem. 25:931-932 (1960), the disclosure of which is hereby incorporated by reference. Column chromatography was run on silica gel (Merck, H 60), and reactions were monitored by TLC on Baker-flex Silica gel IB2-F plates (J. T. Baker). Silver nitrate column chromatography was done on silica gel impregnated with AgNO3 (20% of AgNO3 on silica gel Merck H 60).

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

Procedure: 1-(Tetrahydopyran-2-yloxy)-4-pentyne (1) (0.66 g, 3.90 mmol) was metallated with n-butyllithium solution (2.5M) in hexane (1.87 ml, 1.2 eq.). Addition of a solution of n-pentyl bromide (0.725 ml, 1.5 eq.) in DMPU (2 ml) produced 0.54 g (58% yield) of the title compound (15). 1H NMR (200 MHz) δ: 4.60 (m, 1H, CH-2'), 3.65 (m, 4H, CH2 -1, 6'), 2.26 (tt, J=7.0, 7.0, 2.0, 2.0 Hz, 2H, CH2 -3), 2.13 (tt, J=7.0, 7.0, 2.5, 2.5 Hz, 2H, CH2 -6), 1.77 (tt, J=6.8, 6.8, 7.07 7.0 Hz, 2H, CH2 -2), 1.33 (m, 6H, CH2 -7, 8, 9), 1.52 (m, 6H, CH2 -3', 4', 5'), 0.89 (t, J=7.0 Hz, 3H, CH3). MS [FAB, m/z(%)] 237 (M+ -1), 85 (100). IR (CCl4, cm-1) 2229, 1322, 1331, 1201, 1138, 1121, 1034.

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

Procedure: Hydrazine hydrate and hydrogen peroxide (30 wt. % solution in water) were purchased from Mallinckrodt (Chesterfield, Mo.) and Fisher Chemical Co. (Fair Lawn, N.J.), respectively. Butyllithium (1.6M and 2.5M solutions in hexane), 2-(3-butynyloxy)tetrahydro-2H-pyran (1-(tetrahydopyran-2-yloxy)-3-butyne), lithium tetrahydridoaluminate, borane-methylsulfide complex, Cu(I)Br.Me2S complex, and p-toluenesulfonyl chloride from Aldrich Chemical Co. (Milwaukee, Wis.), and bromine and triphenylphosphine from Fluka Chemical Co. (Ronkonkoma, N.Y.), were used as purchased. 1-(Tetrahydopyran-2-yloxy)-4-pentyne was prepared from the corresponding alcohol using the methods described in Robertson, "Adducts of tert-alcohols containing an ethynyl group with dihydropyran. Potentially useful intermediates," J. Org. Chem. 25:931-932 (1960), the disclosure of which is hereby incorporated by reference. Column chromatography was run on silica gel (Merck, H 60), and reactions were monitored by TLC on Baker-flex Silica gel IB2-F plates (J. T. Baker). Silver nitrate column chromatography was done on silica gel impregnated with AgNO3 (20% of AgNO3 on silica gel Merck H 60).