3-Isoxazolidinone, 4,4-dimethyl-

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: By the method of Example 6, Step B, 95.6 g (0.83 mole) of 4,4-dimethyl-3-isoxazolidinone, 186 g (0.83 mole) of 2-chloro-4-fluorobenzyl bromide, 114.7 g (0.83 mole) of potassium carbonate, and 2.2 g (0.008 mole) of 1,4,7,10,13,16-hexaoxacyclooctadecane were reacted at room temperature in 1500 ml of acetonitrile, yielding 230 g of impure 2-[(2-chloro-4-fluorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone. The nmr spectrum was consistent with the proposed structure.

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

Procedure: A mixture of 4-picolyl chloride hydrochloride (1.4 g, 0.0084 mol), 4,4-dimethyl-3-isoxazolidinone (1.0 g, 0.0084 mol), potassium carbonate (3.6 g, 0.0261 mol), and 18-Crown-6 (0.10 g, 0.0004 mol) in acetonitrile (50 mL) is stirred at room temperature overnight. The reaction mixture is poured into ethyl acetate (50 mL) and the mixture washed with water (3×30 mL). The organic layer is dried (magnesium sulfate) and concentrated under reduced pressure to yield an oil. This oil is passed through a silica gel pad eluting with 4:1 chloroform:methanol. The filtrate is concentrated and converted to 1.4 g of the maleate salt of the title compound. the mixture washed with water (3×30 mL) The organic layer is dried (magnesium sulfate) concentrated under reduced pressure to yield an oil eluting with 4:1 chloroform The filtrate is concentrated

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

Procedure: By the method of Example 6, Step B, 95.6 g (0.83 mole) of 4,4-dimethyl-3-isoxazolidinone, 186 g (0.83 mole) of 2-chloro-4-fluorobenzyl bromide, 114.7 g (0.83 mole) of potassium carbonate, and 2.2 g (0.008 mole) of 1,4,7,10,13,16-hexaoxacyclooctadecane were reacted at room temperature in 1500 ml of acetonitrile, yielding 230 g of impure 2-[(2-chloro-4-fluorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone. The nmr spectrum was consistent with the proposed structure.

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 mixture of 2-chloro-6-nitrobenzyl bromide (17.5 g, 0.07 mole), 4,4-dimethyl-3-isoxazolidinone (11.5 g, 0.1 mole), potassium carbonate (13.8 g, 0.1 mole), and 1,4,7,10,13,16-hexaoxacyclooctadecane (0.5 g, 0.002 mole) in acetonitrile (500 ml) was stirred at ambient temperature overnight. The reaction mixture was poured into ethyl acetate (500 ml) and the mixture washed with water (3×200 ml). The dried (magnesium sulfate) ethyl acetate layer was concentrated under reduced pressure to yield a liquid. The liquid product was subjected to chromatography on silica gel, eluting with 1:9 ethyl acetate:heptane. The appropriate fractions were combined and concentrated under reduced pressure to yield a white solid. The solid was recrystallized from ethyl acetate to yield 10.5 g of 2-[(2-chloro-6-nitrophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, m.p. 86°-88° C. the mixture washed with water (3×200 ml) The dried (magnesium sulfate) ethyl acetate layer was concentrated under reduced pressure to yield a liquid eluting with 1:9 ethyl acetate concentrated under reduced pressure to yield a white solid The solid was recrystallized from ethyl acetate