prop-2-enyl 2-bromoacetate

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: Potassium carbonate (1.53 g) was added to an acetonitrile (10 mL) solution of 3-(2,6-difluorophenyl)-pyrazole (1 g) and allyl 2-bromoacetate (1.49 g), and refluxed for 3 hours. The resulting product was extracted with acetate and diluted hydrochloric acid added thereto at room temperature. The organic layer was dried over anhydrous magnesium sulfate and concentrated, and the resulting concentrate was purified through silica gel column chromatography (chloroform) to obtain allyl 2-{3-(2,6-difluorophenyl)pyrazol-1-yl}acetate (1.5 g). refluxed for 3 hours The resulting product was extracted with acetate and diluted hydrochloric acid added at room temperature The organic layer was dried over anhydrous magnesium sulfate concentrated the resulting concentrate was purified through silica gel column chromatography (chloroform)

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

Procedure: Under a nitrogen atmosphere, sodium hydride (6.41 g, 0.267 mol) and THF (125 ml) were combined and the suspension was cooled to -15° C. A THF solution (150 ml) of (phenylsulfonyl)acetone (50 g, 0.253 mol) was added to the suspension in a dropwise fashion over an hour. The resultant mixture was stirred for an additional 20 minutes at -15° C. Allyl bromoacetate (47.5 g, 0.265 mol) dissolved in THF (100 ml) was added in a dropwise fashion to the mixture over a period of 30 minutes while maintaining the temperature of the solution below 0° C. The resultant solution was stirred at -5° C. for 15 minutes, allowed to warm to room temperature over a period of an hour, and stirred overnight at room temperature. The reaction solution was poured into saturated aqueous ammonium chloride solution (800 ml) and chloroform (500 ml) and the aqueous layer was separated and extracted with chloroform (2X, 200 ml). The chloroform layers were combined and washed with saturated aqueous sodium chloride (1X, 350 ml), dried over sodium sulfate, filtered and concentrated in vacuo to an oil. The oil was crystallized from a mixture of ethyl acetate and hexane. The collected solid was washed with cold 1:3 ethyl acetate: hexane and dried in vacuo, yielding 52.9 g of the allyl 3-(phenylsulfonyl)-4-oxopentanoate: n.m.r. (90 MHz, CDCl3): δ 2.51 (s, 3), 2.97 (n, 2,), 4.51 (dm, 2, J=6), 4.65 (m, 1), 5.1-5.19 (m,2), 5.58-6.00 (m, 1), 7.4-7.8 (m, 5); m.p. 62-64° C. was added in a dropwise fashion to the mixture over a period of 30 minutes while maintaining the temperature of the solution below 0° C to warm to room temperature over a period of an hour the aqueous layer was separated extracted with chloroform (2X, 200 ml) washed with saturated aqueous sodium chloride (1X, 350 ml) dried over sodium sulfate filtered concentrated in vacuo to an oil The oil was crystallized from a mixture of ethyl acetate and hexane The collected solid was washed with cold 1:3 ethyl acetate hexane and dried in vacuo

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

Procedure: Potassium carbonate (1.53 g) was added to an acetonitrile (10 mL) solution of 3-(2,6-difluorophenyl)pyrazole (1 g) and allyl 2-bromoacetate (1.49 g), and refluxed for 3 hours. The resulting product was extracted with acetate and diluted hydrochloric acid added thereto at room temperature. The organic layer was dried over anhydrous magnesium sulfate and concentrated, and the resulting concentrate was purified through silica gel column chromatography (chloroform) to obtain allyl 2-{3-(2,6-difluorophenyl)pyrazol-1-yl}acetate (1.5 g). refluxed for 3 hours The resulting product was extracted with acetate and diluted hydrochloric acid added at room temperature The organic layer was dried over anhydrous magnesium sulfate concentrated the resulting concentrate was purified through silica gel column chromatography (chloroform)

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

Procedure: The tritylthioazetidinone 2 is treated with 1.5 equivalents of allyl bromoacetate and powdered potassium hydroxide in benzene solvent at ambient temperature in the presence of dicyclohexyl-18-crown-6 for 4 hours. The resulting (3S,4R)-1-(allyloxycarbonyl)methyl-3-[(R)-1-(tert-butyldimethylsiloxy)ethyl]-4-triphenylmethylthio-2-azetidinone (3) is isolated by conventional means. Alternatively p-nitro-benzylbromoacetate may be substituted for allylbromoacetate.

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

Procedure: The tritylthioazetidinone 2 is treated with 1.5 equivalents of allyl bromoacetate and powdered potassium hydroxide in benzene solvent at ambient temperature in the presence of dicyclohexyl-18-crown-6 for 4 hours. The resulting (3S,4R)-1-(allyloxycarbonyl)methyl-3-[(R)-1-(tert-butyldimethylsiloxy)ethyl]-4-triphenylmethylthio-2-azetidinone (3) is isolated by conventional means. Alternatively p-nitro-benzylbromoacetate may be substituted for allylbromoacetate.

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

Procedure: Potassium carbonate (1.53 g) was added to an acetonitrile (10 mL) solution of 3-(2,6-difluorophenyl)-pyrazole (1 g) and allyl 2-bromoacetate (1.49 g), and refluxed for 3 hours. The resulting product was extracted with acetate and diluted hydrochloric acid added thereto at room temperature. The organic layer was dried over anhydrous magnesium sulfate and concentrated, and the resulting concentrate was purified through silica gel column chromatography (chloroform) to obtain allyl 2-(3-(2,6-difluorophenyl)pyrazol-1-yl)acetate (1.5 g). refluxed for 3 hours The resulting product was extracted with acetate and diluted hydrochloric acid added at room temperature The organic layer was dried over anhydrous magnesium sulfate concentrated the resulting concentrate was purified through silica gel column chromatography (chloroform)

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

Procedure: Potassium carbonate (1.53 g) was added to an acetonitrile (10 mL) solution of 3-(2,6-difluorophenyl)-pyrazole (1 g) and allyl 2-bromoacetate (1.49 g), and refluxed for 3 hours. The resulting product was extracted with acetate and diluted hydrochloric acid added thereto at room temperature. The organic layer was dried over anhydrous magnesium sulfate and concentrated, and the resulting concentrate was purified through silica gel column chromatography (chloroform) to obtain allyl 2-(3-(2,6-difluorophenyl)pyrazol-1-yl)acetate (1.5 g). refluxed for 3 hours The resulting product was extracted with acetate and diluted hydrochloric acid added at room temperature The organic layer was dried over anhydrous magnesium sulfate concentrated the resulting concentrate was purified through silica gel column chromatography (chloroform)

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

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

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

Procedure: Under a nitrogen atmosphere, sodium hydride (6.41 g, 0.267 mol) and THF (125 ml) were combined and the suspension was cooled to -15° C. A THF solution (150 ml) of (phenylsulfonyl)acetone (50 g, 0.253 mol) was added to the suspension in a dropwise fashion over an hour. The resultant mixture was stirred for an additional 20 minutes at -15° C. Allyl bromoacetate (47.5 g, 0.265 mol) dissolved in THF (100 ml) was added in a dropwise fashion to the mixture over a period of 30 minutes while maintaining the temperature of the solution below 0° C. The resultant solution was stirred at -5° C. for 15 minutes, allowed to warm to room temperature over a period of an hour, and stirred overnight at room temperature. The reaction solution was poured into saturated aqueous ammonium chloride solution (800 ml) and chloroform (500 ml) and the aqueous layer was separated and extracted with chloroform (2X, 200 ml). The chloroform layers were combined and washed with saturated aqueous sodium chloride (1X, 350 ml), dried over sodium sulfate, filtered and concentrated in vacuo to an oil. The oil was crystallized from a mixture of ethyl acetate and hexane. The collected solid was washed with cold 1:3 ethyl acetate:hexane and dried in vacuo, yielding 52.9 g of the allyl 3-(phenylsulfonyl)-4-oxopentanoate: n.m.r. (90 MHz, CDCl3): δ 2.51 (s, 3), 2.97 (n, 2,), 4.51 (dm, 2, J=6), 4.65 (m, 1), 5.1-5.19 (m,2), 5.58-6.00 (m, 1), 7.4-7.8 (m, 5); m.p. 62-64° C. was added in a dropwise fashion to the mixture over a period of 30 minutes while maintaining the temperature of the solution below 0° C to warm to room temperature over a period of an hour the aqueous layer was separated extracted with chloroform (2X, 200 ml) washed with saturated aqueous sodium chloride (1X, 350 ml) dried over sodium sulfate filtered concentrated in vacuo to an oil The oil was crystallized from a mixture of ethyl acetate and hexane The collected solid was washed with cold 1:3 ethyl acetate hexane and dried in vacuo