oxetan-3-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:

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:

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

Procedure: To a suspension of oxetan-3-ol (100 mg, 1.35 mmol) in tetrahydrofuran (1 mL) and N,N-dimethylformamide (1 mL) was added 60% sodium hydride in mineral oil (81 mg, 2.03 mmol). The mixture was stirred for 30 minutes at room temperature. The reaction was then cooled to 0° C. and a solution of 2,4-dichloropyrimidine (300 mg, 2.03 mmol) in tetrahydrofuran (1 mL) and N,N′-dimethylformamide (1 mL) was added. The mixture was warmed to room temperature and stirred for 24 h. The reaction was then diluted with ethyl acetate (20 mL) and washed with 1:1 water:brine (3×40 mL). The organic extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by Chromatography on silica gel (10-60% ethyl acetate in hexanes) to afford 2-chloro-4-(oxetan-3-yloxy)pyrimidine (91 mg, 0.49 mmol, 36% yield) as a white solid. MS ESI: [M+H]+ m/z 186.8. The reaction was then cooled to 0° C. The mixture was warmed to room temperature stirred for 24 h washed with 1:1 water The organic extracts were dried over sodium sulfate filtered concentrated under reduced pressure The resulting residue was purified by Chromatography on silica gel (10-60% ethyl acetate in hexanes)

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

Procedure: A mixture of 0.76 g (19 mmol) of 60 percent in mineral oil sodium hydride in dry N,N-dimethylformamide was prepared in a flask under a nitrogen blanket and to it was added 2.02 g (8.0 mmol) of 2-chloro-3-fluoro-4-methylsulfonylbenzoic acid in portions with stirring at ambient temperature. The mixture was allowed to cool and then 0.71 g (9.6 mmol) of 3-hydroxyoxetane was added dropwise with stirring. There was an exotherm. After one hour, the reaction appeared to be complete and water was added cautiously. The resulting aqueous solution was extracted with ether and was then acidified with 1N aqueous hydrochloric acid. The resulting mixture was extracted three times with ethyl acetate and the three extracts were combined, washed with water, dried over magnesium sulfate, and concentrated by evaporation under reduced pressure. The residue was crystallized with a mixture of acetone and hexane to obtain 1.41 g of the title compound as white crystals melting at 180-183° C. was prepared in a flask under a nitrogen blanket to cool with stirring The resulting aqueous solution was extracted with ether The resulting mixture was extracted three times with ethyl acetate washed with water dried over magnesium sulfate concentrated by evaporation under reduced pressure The residue was crystallized with a mixture of acetone and hexane

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To oxetan-3-ol (112 mg, 1.5 mmol) in THF (5 mL) was added 4-bromophenol (200 mg, 1.16 mmol), polymeric triphenylphosphine (0.5 g, 1.5 mmol) and DIAD (305 mg, 1.5 mmol). The reaction mixture was degassed with nitrogen for 2 min and stirred at 110° C. for 17 hours. The cooled reaction mixture was filtered and the filtrate was concentrated in vacuo to give a residue, which was dissolved in ethyl acetate (50 mL) and washed with 2M NaOH (3×15 mL) and brine (2×20 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo to give a residue, which was purified by flash chromatography on silica gel eluting with EtOAc/petroleum ether (1:10) to give 3-(4-bromophenoxy)oxetane (140 mg, 53%) as a colorless solid. 1H NMR (400 MHz, CDCl3) δ 7.37 (d, 2H), δ 6.55 (d, 2H), 5.19-5.13 (m, 1H), 4.97-4.94 (m, 2H), 4.76-4.73 (m, 2H). The reaction mixture was degassed with nitrogen for 2 min The cooled reaction mixture was filtered the filtrate was concentrated in vacuo to give a residue, which washed with 2M NaOH (3×15 mL) and brine (2×20 mL) The organic layer was dried over Na2SO4 concentrated in vacuo to give a residue, which was purified by flash chromatography on silica gel eluting with EtOAc/petroleum ether (1:10)

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

Procedure: A mixture of 12.9 g of 2-isopropylthiobenzoyl chloride and 20 ml of absolute toluene is added dropwise to a mixture of 4.44 g of 3-hydroxyoxetane, 6.64 g of pyridine and 60 ml of absolute toluene at a temperature of 15° to 20° C. The suspension formed is stirred at a temperature of 20°-25° C. for 2 hours and at a temperature of 40°-45° C. for a further 3 hours. Adding water to the reaction mixture, washing the organic phase with water and drying and evaporating it gives 12.6 g of oxetan-3-yl 2-isopropylthiobenzoate as a pale yellow oil. The suspension formed Adding water to the reaction mixture, washing the organic phase with water drying evaporating it

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

Procedure: A mixture of 12.9 g of 2-isopropylthiobenzoyl chloride and 20 ml of absolute toluene is added dropwise to a mixture of 4.44 g of 3-hydroxyoxetane, 6.64 g of pyridine and 60 ml of absolute toluene at a temperature of 15° to 20° C. The suspension formed is stirred at a temperature of 20°-25° C. for 2 hours and at a temperature of 40°-45° C. for a further 3 hours. Adding water to the reaction mixture, washing the organic phase with water and drying and evaporating it gives 12.6 g of oxetan-3-yl 2-isopropylthiobenzoate as a pale yellow oil. The suspension formed Adding water to the reaction mixture, washing the organic phase with water drying evaporating it