2-HYDROXYTETRAHYDROFURAN

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: 0.55 Gram of 2-(4,6-dimethoxypyrimidin-2-yl)oxybenzoic acid, 0.21 g of tetrahydrofuryl alcohol and 0.85 g of 2,4,6-triisopropylbenzenesulfonyl chloride were dissolved in 5 ml of tetrahydrofuran. Subsequently, 0.45 g of 1-methylimidazole was added to the mixture. After stirring the resulting solution at room temperature for 1 hour in order to carry out the reaction, the reaction solution was poured into diluted hydrochloric acid, and exracted with ethyl acetate. The organic layer separated from the aqueous layer was washed with saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue obtained was subjected to silica gel column chromatography (mfd. by Merch & Co., Inc., solvent: chloroform) to obtain 0.30 g of tetrahydrofurfuryl 2-(4,6-dimethoxypyrimidin-2-yl)oxybenzoate [present compound (III-9)]. the reaction The organic layer separated from the aqueous layer was washed with saturated sodium chloride solution dried over anhydrous magnesium sulfate The solvent was removed under reduced pressure the residue obtained

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 4 g of benzyltriphenylphosphonium chloride in 20 ml of tetrahydrofuran was added 7.07 ml of 1.6M hexane solution of n-butyl lithium under cooling at 0° C. After stirring at room temperature for 30 minutes, 1 g of 2-hydroxytetrahydrofuran was added, followed by stirring at room temperature for 16 hours. Subsequently, after refluxing for 2 hours, insolubles were filtered off and the solvent was distilled off. The residue was purified by silica gel column chromatography (solvent: hexane-ethyl acetate=2:1) to give 2 g of (E)-5-phenyl-4-penten-1-ol as a colorless oily substance. by stirring at room temperature for 16 hours Subsequently, after refluxing for 2 hours insolubles were filtered off the solvent was distilled off The residue was purified by silica gel column chromatography (solvent: hexane-ethyl acetate=2:1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 4 g of benzyltriphenylphosphonium chloride in 20 ml of tetrahydrofuran was added 7.07 ml of 1.6M hexane solution of n-butyl lithium under cooling at 0° C. After stirring at room temperature for 30 minutes, 1 g of 2-hydroxytetrahydrofuran was added, followed by stirring at room temperature for 16 hours. Subsequently, after refluxing for 2 hours, insolubles were filtered off and the solvent was distilled off. The residue was purified by silica gel column chromatography (solvent: hexane-ethyl acetate=2:1) to give 2 g of (E)-5-phenyl-4-penten-1-ol as a colorless oily substance. by stirring at room temperature for 16 hours Subsequently, after refluxing for 2 hours insolubles were filtered off the solvent was distilled off The residue was purified by silica gel column chromatography (solvent: hexane-ethyl acetate=2:1)

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:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of 6.28 g (0.015) mol) of amoxicillin trihydrate in 150 ml of distilled water was added in one portion 15 ml of 1 N aqueous sodium hydroxide solution. The amoxicillin quickly dissolved and after two minutes 2.25 g (0.025 mol) of tetrahydro-2-furanol was added. After stirring at 25° C. for two minutes the solution was quickly frozen by means of a dry ice-acetone bath and then lyophilized for 22 hr. The resulting product {2S-[2α, 5α, 6β(S*)]}-6-{[2-tetrahydrofuranylamino(4-hydroxyphenyl)acetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid sodium salt (6.55 g) was obtained as a white powder. was added was quickly frozen by means of a dry ice-acetone bath lyophilized for 22 hr

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

Procedure: Following the general procedure for the methylenation of lactols via Wittig-olefination (Description 4, Method A), 100 g (280 mmol) of methyltriphenylphosphonium bromide was reacted overnight at room temperature with 270 mL (270 mmol) of a one molar (1.0 M) solution of potassium tert-butoxide (KOtBu) in 350 mL of anhydrous tetrahydrofuran (THF). The phosphorane was subsequently reacted in situ at ca. 0° C. (ice bath) with 29.7 g (134 mmol) of (2R/S)(3R/S)-4,4-dimethyl-3-phenylmethoxy)oxolan-2-ol (2b) dissolved in 150 mL of anhydrous tetrahydrofuran (THF). After work-up and isolation, followed by repeated titruation of residual triphenylphosphine oxide (Ph3PO) with methyl tert-butyl ether (MTBE) and hexane (Hxn) mixtures, i.e. MTBE/Hxn ˜1:2 (v/v) at ca. −20° C. (freezer), the crude product was obtained. Purification by silica gel column chromatography using ethyl acetate (EtOAc) and hexane (Hxn) mixtures as eluent (EtOAc/Hxn=1:4→EtOAc/Hxn=1:3→EtOAc/Hxn=1:2) provided 18.0 g (61% yield) of the title compound (2) as a colorless liquid. Rf=0.63 (EtOAc/Hxn=1:3). MS (ESI) m/z: 221.1 (M+H)+, 243.1 (M+Na)+. The analytical data was consistent with the proposed structure, with the corresponding material (1) obtained starting from enantiopure D-pantolactone, and with the data reported in the literature (Mandel et al., Org. Lett. 2004, 6(26), 4801-4803; and Ito et al., Synthesis 1993, 137-140). at ca. −20° C. the crude product was obtained Purification by silica gel column chromatography

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

Procedure: Following the general procedure for the methylenation of lactols via Wittig-olefination (Description 4, Method A), 408 g (1.14 mmol) of freshly powdered methyltriphenylphosphonium bromide was reacted for six hours at room temperature with 1.1 L (1.1 mol) of a one molar (1 M) solution of potassium tert-butoxide (KOtBu) in 1 L of anhydrous tetrahydrofuran (THF). The phosphorane was subsequently reacted in situ at ca. −78° C. (dry ice/isopropanol bath) with 84.6 g (381 mmol) of (2R/S)(3R)-4,4-dimethyl-3-phenylmethoxy)oxolan-2-ol (1b) dissolved in 200 mL of anhydrous tetrahydrofuran (THF). After work-up and isolation, the crude product was purification in four portions by silica gel column chromatography using ethyl acetate (EtOAc) and n-heptane (Hptn) mixtures as eluent (EtOAc/Hptn=1:4) to provide 48.6 g (58% yield) of the title compound (1) as a colorless oil. Rf=0.35 (EtOAc/Hxn=1:4); 0.19 (EtOAc/Hxn=1:6). 1H NMR (400 MHz, CDCl3): δ=0.91 (s, 3H), 0.92 (s, 3H), 2.83 (t, J=6.0 Hz, 1H), 3.38 (dd, J=10.8, 6.0 Hz, 1H), 3.55 (dd, J=10.8, 6.4 Hz, 1H), 3.63 (d, J=8.4 Hz, 1H), 4.31 (d, J=12.0 Hz, 1H), 4.62 (d, J=11.6 Hz, 1H), 5.26 (ddd, J=17.0, 2.0, 0.8 Hz, 1H), 5.38 (ddd, J=10.6, 1.6, 0.8 Hz, 1H), 5.81 (ddd, J=17.2, 10.4, 8.4 Hz, 1H), 7.27-7.38 (m, 5H) ppm. MS (ESI) m/z: 221.1 (M+H)+. The analytical data was consistent with the proposed structure and with the data reported in the literature (Mandel et al., Org. Lett. 2004, 6(26), 4801-4803; and Ito et al., Synthesis 1993, 137-140). purification in four portions by silica gel column chromatography