[3-(bromomethyl)oxetan-3-yl]methanol

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: A solution of 42 g (0.23 mol) of [3-(bromomethyl)oxetan-3-yl] methanol (produced according to Example 1) in 420 ml of ethanol was refluxed with 13 g (0.265 mol) of sodium cyanide for 18 hours. After cooling to room temperature, the precipitated sodium bromide was filtered off and the filtrate concentrated by evaporation. The residue was distilled at 0.4 torr. The yield of product as a colorless oil was 16 g (54 percent). The boiling point of the product was 107° C./0.4 torr. Other data concerning the product was: the precipitated sodium bromide was filtered off the filtrate concentrated by evaporation The residue was distilled at 0.4 torr was 107° C.

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

Procedure: A solution of sodium azide (2.07 g, 0.0317 mol), 3-bromomethyl-3-hydroxymethyloxetane (5.0 g, 0.028 mol) and tetra-n-butylammonium bromide (0.0978 g, 0.3 mmol) in water (14 mL) was heated for 3 h at 104°-107° C. The solution was cooled and was extracted with ethyl ether (5×20 mL). The combined extracts were evaporated to give 1.92 g (49%) of 3-azidomethyl-3-hydroxymethyloxetane, essentially pure by glc analysis, as an oil. NMR: 1H NMR: 3.70 (s, 2H), 3.84 (d, J=4.9 Hz, 2H), 4.44 (s, 4H); 13C NMR: 44.283, 53.852, 64.073, 76.227. The solution was cooled was extracted with ethyl ether (5×20 mL) The combined extracts were evaporated

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

Procedure: A solution of sodium azide (2.07 g, 0.0317 mol), 3-bromomethyl-3-hydroxymethyloxetane (5.0 g, 0.028 mol) and tetra-n-butylammonium bromide (0.0978 g, 0.3 mmol) in water (14 mL) was heated for 3 h at 104°-107° C. The solution was cooled and was extracted with ethyl ether (5×20 mL). The combined extracts were evaporated to give 1.92 g (49%) of 3-azidomethyl-3-hydroxymethyloxetane, essentially pure by glc analysis, as an oil. NMR: 1H NMR: 3.70 (s, 2H), 3.84 (d, J=4.9 Hz, 2H), 4.44 (s, 4H); 13C NMR: 44.283, 53.852, 64.073, 76.227. The solution was cooled was extracted with ethyl ether (5×20 mL) The combined extracts were evaporated

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

Procedure: As such, it has been discovered that monofunctional azidooxetane compounds, i.e., 3-azidomethyl-3-R1 -oxetanes, can also be prepared by combining a neat halooxetane with an aqueous metallic azide solution and a phase transfer catalyst (PTC). For example, using the process of the present invention, 3-chloromethyl-3-methyloxetane gives the corresponding 3-azidomethyl-3-methyloxetane (AMMO) in 97% yield. Moreover, 3-bromomethyl-3-hydroxymethyloxetane was previously converted to the corresponding 3-azidomethyl-3-hydroxymethyloxetane in acetone. Using the process of the present invention, however, 3-bromomethyl-3-hydroxymethyloxetane is converted to the corresponding 3-azidomethyl-3-hydroxymethyloxetane, without the use of an organic solvent, using an aqueous sodium azide solution and a phase transfer catalyst. The process of the present invention gives the same result with a faster rate of reaction and without the use of an organic solvent. In addition, 3-chloromethyl-3-methyloxetane 3-chloromethyl-3-phenoxymethyloxetane reacts with an aqueous solution of sodium azide in water with a PTC to give 3-azidomethyl-3-phenoxymethyloxetane in 87% yield. The process of the present invention gives the same result with a faster rate of reaction and without the use of an organic solvent

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

Procedure: As such, it has been discovered that monofunctional azidooxetane compounds, i.e., 3-azidomethyl-3-R1 -oxetanes, can also be prepared by combining a neat halooxetane with an aqueous metallic azide solution and a phase transfer catalyst (PTC). For example, using the process of the present invention, 3-chloromethyl-3-methyloxetane gives the corresponding 3-azidomethyl-3-methyloxetane (AMMO) in 97% yield. Moreover, 3-bromomethyl-3-hydroxymethyloxetane was previously converted to the corresponding 3-azidomethyl-3-hydroxymethyloxetane in acetone. Using the process of the present invention, however, 3-bromomethyl-3-hydroxymethyloxetane is converted to the corresponding 3-azidomethyl-3-hydroxymethyloxetane, without the use of an organic solvent, using an aqueous sodium azide solution and a phase transfer catalyst. The process of the present invention gives the same result with a faster rate of reaction and without the use of an organic solvent. In addition, 3-chloromethyl-3-methyloxetane 3-chloromethyl-3-phenoxymethyloxetane reacts with an aqueous solution of sodium azide in water with a PTC to give 3-azidomethyl-3-phenoxymethyloxetane in 87% yield. The process of the present invention gives the same result with a faster rate of reaction and without the use of an organic solvent

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 18.1 g of 1A and 11.7 g of benzylamine were mixed with 5 ml of water and the resulting mixture was stirred at 100° C. After 4 hours the solution was allowed to cool to ambient temperature and 13.8 ml of 36% (w/w) hydrochloric acid was added. The resulting mixture was stirred at 60° C. After 2 hours the solution was again allowed to cool to room temperature and then washed with dichloromethane to remove by-products. The aqueous layer was made alkaline by the addition of a solution of 5.5 g of sodium hydroxide in 10 ml of water and stirred at 100° C. for 1 hour. After cooling to ambient temperature the pH of the mixture was raised by addition of another solution of 5.5 g of sodium hydroxide in 10 ml of water and washed with hexane to remove benzylamine. The water was evaporated under reduced pressure, and the solid residue was taken up in dichloromethane. Inorganic salts, which remained undissolved, were removed by filtration, and the dichloromethane was evaporated in vacuo, leaving 1, as a white crystalline solid. to cool to ambient temperature The resulting mixture was stirred at 60° C After 2 hours the solution was again allowed to cool to room temperature washed with dichloromethane to remove by-products by the addition of a solution of 5.5 g of sodium hydroxide in 10 ml of water stirred at 100° C. for 1 hour After cooling to ambient temperature the pH of the mixture was raised by addition of another solution of 5.5 g of sodium hydroxide in 10 ml of water washed with hexane to remove benzylamine The water was evaporated under reduced pressure were removed by filtration the dichloromethane was evaporated in vacuo leaving 1

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-nitro-1H-pyrazole (0.5 g, 4.42 mmol) and K2CO3 (1.22 g, 8.84 mmol) were suspended in acetonitrile (30 mL) in a 2-necked flask under nitrogen and (3-(bromomethyl)oxetan-3-yl)methanol (1.36 g, 7.52 mmol) was added dropwise. The reaction was heated at 60° C. for 16 h and the solution was concentrated to about ⅓ of the volume under vacuum and then partitioned between DCM (50 mL) and water (50 mL). The organics were dried over Na2SO4, filtered and the solvent evaporated to give (3-((4-nitro-1H-pyrazol-1-yl)methyl)oxetan-3-yl)methanol as a transparent oil (0.94 g, quantitative yield). the solution was concentrated to about ⅓ of the volume under vacuum partitioned between DCM (50 mL) and water (50 mL) The organics were dried over Na2SO4 filtered the solvent evaporated

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

Procedure: 600 mg of 3-chloro-4-hydroxybenzotrifluoride and 829 mg of 3-bromomethyl-3-oxetanemethanol were dissolved in 20 ml of acetonitrile, and 1.49 g of cesium carbonate were added. The reaction mixture was heated to 110° C. and stirred at this temperature for three hours. 50 ml of water and 50 ml of ethyl acetate were added to the cooled reaction mixture. The organic phase was removed, dried over MgSO4 and then concentrated under reduced pressure. The residue was purified on silica gel with the n-heptane/ethyl acetate solvent mixture as a linear gradient of 100% n-heptane=>100% ethyl acetate. This gave 990 mg of [3-(2-chloro-4-trifluoromethylphenoxymethyl)oxetan-3-yl]methanol. The organic phase was removed dried over MgSO4 concentrated under reduced pressure The residue was purified on silica gel with the n-heptane/ethyl acetate solvent mixture as a linear gradient of 100% n-heptane=>100% ethyl acetate