5-(oxan-2-yloxy)pent-2-yn-1-ol

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: A solution of alcohol 8 (6.16 g, 33.5 mmol) and p-toluenesulphonyl chloride (7.36 g, 38.5 mmol) in dry ether (80 mL) was cooled to -10°. Powdered KOH (25 g, 446 mmol) was added in 5 g portions over 20 min. The resulting suspension was stirred at 0° for 45 min, poured into ice-water (200 mL) and extracted with ether (3×100 mL). The combined ether solutions were washed with brine, dried (MgSO4), and concentrated in vacuo. Final traces of solvent were removed by pumping for 6 hr at 0.1 mmHg, yielding 11.23 g of 9 (99%). This was used without further purification. extracted with ether (3×100 mL) The combined ether solutions were washed with brine dried (MgSO4) concentrated in vacuo were removed by pumping for 6 hr at 0.1 mmHg

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

Procedure: A solution of alcohol 8 (6.16 g, 33.5 mmol) and p-toluenesulphonyl chloride (7.36 g, 38.5 mmol) in dry ether (80 mL) was cooled to -10°. Powdered KOH (25 g, 446 mmol) was added in 5 g portions over 20 min. The resulting suspension was stirred at 0° for 45 min, poured into ice-water (200 mL) and extracted with ether (3×100 mL). The combined ether solutions were washed with brine, dried (MgSO4), and concentrated in vacuo. Final traces of solvent were removed by pumping for 6 hr at 0.1 mmHg, yielding 11.23 g of 9 (99%). This was used without further purification. extracted with ether (3×100 mL) The combined ether solutions were washed with brine dried (MgSO4) concentrated in vacuo were removed by pumping for 6 hr at 0.1 mmHg

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

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

Procedure: To a solution of 3.31 g (9.6 mmol) of of 4-(4-hydroxy-benzenesulfonyl)-2,2-dimethyl-thiomorpholine-3-carboxylic acid methyl ester and 2.12 g (11.5nmmol) of 5-(tetrahydro-2H-pyran-2-yloxy)-2-pentyn-1-ol in 15 mL of THF was added 3.0 g (11.5 mmol) of triphenylphosphine, followed by dropwise addition of 1.8 mL (11.5 mmol) of diethyl azodicarboxylate. The resulting solution was stirred at room temperature for 18 h. The reaction was diluted with ethyl acetate, washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with ethyl acetate:hexanes (1:9) to provide 3.03 g (62%) of methyl 2,2-dimethyl-4-[(4-{[5-(tetrahydro-2H-pyran-2-yloxy)-2-pentynyl]oxy}phenyl)sulfonyl]-3-thiomorpholine carboxylate as a colorless oil. Electrospray Mass Spec: 534.4 (M+Na)+ washed with water and brine dried over MgSO4 filtered concentrated in vacuo The residue was chromatographed on silica gel eluting with ethyl acetate:hexanes (1:9)

Conditions: temp:-23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 8.0 mL (51 mmol) of 2-(3-butynyloxy)tetrahydro-2H-pyran in 150 mL of THF under nitrogen atmosphere at −23° C. was added dropwise a solution of 33 mL (53 mmol) of 1.6M butyllithium in hexanes, maintaining the temperature at −23° C. The resulting solution was stirred at 0° C. for 2 h, recooled to −23° C. and 2.4 g (76.5 mmol) of parafomaldehyde was added in several portions. The mixture was stirred at −23° C. for 1h and let warm to room temperature and stirred for 18 h. The reaction mixture was poured into a large excess of ice water and extracted with ether. The organics were washed with brine until neutral, dried over MgSO4, filtered and concentrated in vacuo. The residue was kugelrohr distilled to provide 7.26 g (77%) of 5-(tetrahydro-2H-pyran-2-yloxy)-2-pentyn-1-ol as a colorless liquid. EI Mass Spec: 185.1 (M+H)+ recooled to −23° C. 2.4 g (76.5 mmol) of parafomaldehyde was added in several portions let warm to room temperature stirred for 18 h extracted with ether The organics were washed with brine until neutral, dried over MgSO4 filtered concentrated in vacuo The residue was kugelrohr distilled

Conditions: temp:-23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 8.0 mL (51 mmol) of 2-(3-butynyloxy)tetrahydro-2H-pyran in 150 mL of THF under nitrogen atmosphere at −23° C. was added dropwise a solution of 33 mL (53 mmol) of 1.6M butyllithium in hexanes, maintaining the temperature at −23° C. The resulting solution was stirred at 0° C. for 2 h, recooled to −23° C. and 2.4 g (76.5 mmol) of parafomaldehyde was added in several portions. The mixture was stirred at −23° C. for 1h and let warm to room temperature and stirred for 18 h. The reaction mixture was poured into a large excess of ice water and extracted with ether. The organics were washed with brine until neutral, dried over MgSO4, filtered and concentrated in vacuo. The residue was kugelrohr distilled to provide 7.26 g (77%) of 5-(tetrahydro-2H-pyran-2-yloxy)-2-pentyn-1-ol as a colorless liquid. EI Mass Spec: 185.1 (M+H)+ recooled to −23° C. 2.4 g (76.5 mmol) of parafomaldehyde was added in several portions let warm to room temperature stirred for 18 h extracted with ether The organics were washed with brine until neutral, dried over MgSO4 filtered concentrated in vacuo The residue was kugelrohr distilled

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

Procedure: To a solution of 3.31 g (9.6 mmol) of 4-(4-hydroxy-benzenesulfonyl)-2,2-dimethyl-thiomorpholine-3-carboxylic acid methyl ester and 2.12 g (11.5 mmol) of 5-(tetrahydro-2H-pyran-2-yloxy)-2-pentyn-1-ol in 15 mL of THF was added 3.0 g (11.5 mmol) of triphenylphosphine, followed by dropwise addition of 1.8 mL (11.5 mmol) of diethyl azodicarboxylate. The resulting solution was stirred at room temperature for 18 h. The reaction was diluted with ethyl acetate, washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with ethyl acetate:hexanes (1:9) to provide 3.03 g (62%) of methyl 2,2-dimethyl-4-[(4-{[5-(tetrahydro-2H-pyran-2-yloxy)-2-pentynyl]oxy}phenyl)sulfonyl]-3-thiomorpholine carboxylate as a colorless oil. washed with water and brine dried over MgSO4 filtered concentrated in vacuo The residue was chromatographed on silica gel eluting with ethyl acetate:hexanes (1:9)

Conditions: temp:-23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 8.0 mL (51 mmol) of 2-(3-butynyloxy)tetrahydro-2H-pyran in 150 mL of THF under nitrogen atmosphere at −23° C. was added dropwise a solution of 33 mL (53 mmol) of 1.6M butyllithium in hexanes, maintaining the temperature at −23° C. The resulting solution was stirred at 0° C. for 2 h, recooled to −23° C. and 2.4 g (76.5 mmol) of paraformaldehyde was added in several portions. The mixture was stirred at −23° C. for 1 h and let warm to room temperature and stirred for 18 h. The reaction mixture was poured into a large excess of ice water and extracted with ether. The organics were washed with brine until neutral, dried over MgSO4, filtered and concentrated in vacuo. The residue was kugelrohr distilled to provide 7.26 g (77%) of 5-(tetrahydro-2H-pyran-2-yloxy)-2-pentyn-1-ol as a colorless liquid. EI Mass Spec: 185.1 (M+H)+. recooled to −23° C. The mixture was stirred at −23° C. for 1 h let warm to room temperature stirred for 18 h extracted with ether The organics were washed with brine until neutral, dried over MgSO4 filtered concentrated in vacuo The residue was kugelrohr distilled

Conditions: temp:-23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 8.0 mL (51 mmol) of 2-(3-butynyloxy)tetrahydro-2H-pyran in 150 mL of THF under nitrogen atmosphere at −23° C. was added dropwise a solution of 33 mL (53 mmol) of 1.6M butyllithium in hexanes, maintaining the temperature at −23° C. The resulting solution was stirred at 0° C. for 2 h, recooled to −23° C. and 2.4 g (76.5 mmol) of paraformaldehyde was added in several portions. The mixture was stirred at −23° C. for 1 h and let warm to room temperature and stirred for 18 h. The reaction mixture was poured into a large excess of ice water and extracted with ether. The organics were washed with brine until neutral, dried over MgSO4, filtered and concentrated in vacuo. The residue was kugelrohr distilled to provide 7.26 g (77%) of 5-(tetrahydro-2H-pyran-2-yloxy)-2-pentyn-1-ol as a colorless liquid. El Mass Spec: 185.1 (M+H)+ recooled to −23° C. The mixture was stirred at −23° C. for 1 h let warm to room temperature stirred for 18 h extracted with ether The organics were washed with brine until neutral, dried over MgSO4 filtered concentrated in vacuo The residue was kugelrohr distilled

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

Procedure: A solution of compound 3 and imidazole in CH2Cl2 was treated with TBDPSCl dropwise at 0° C. for 2 h. The reaction mixture was diluted with CH2Cl2 (300 mL) and washed with water (200 mL). The organic layer was dried over MgSO4 and concentrated. The residue was purified with 10% EtOAc in hexanes by silica gel column chromatography to give 18.0 g of compound 4 (42.6 mmol, 96% yield): 1H NMR (CDCl3) δ 7.80˜7.64 (m, 4H), 7.49˜7.34 (m, 6H), 4.63 (t, J=3.6 Hz, 1H), 4.31 (t, J=1.9 Hz, 2H), 3.93˜3.83 (m, 1H), 3.77 (dt, J=9.7, 7.1 Hz, 1H), 3.55˜3.44 (m, 2H), 2.48 (tt, J=7.1, 2.1 Hz, 2H), 1.89˜1.46 (m, 6H), 1.06 (s, 9H). washed with water (200 mL) The organic layer was dried over MgSO4 concentrated The residue was purified with 10% EtOAc in hexanes by silica gel column chromatography