chloromethyl 2-propylpentanoate

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

Procedure: Para-formaldehyde (1 g) and zinc chloride (catalytic amount) were mixed together at 0° C. 2,2-Di-n-propylacetyl chloride (30 mole, 4.88 g) was added dropwise over 1 hour. The reaction was warmed to ambient temperature, then was heated to 50-55° C. for 6 hours. The reaction mixture continued stirring at room temperature for 16 hours. The reaction mixture was taken up with methylene chloride (5 mL) and flash chromatographed on 150 g silica gel. Elution with 1 to 5% ethyl acetate/hexane gave 3.3 g (58%) of the desired product. was heated to 50-55° C. for 6 hours chromatographed on 150 g silica gel Elution with 1 to 5% ethyl acetate/hexane

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of the starting [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)ethyl]phosphonic acid (26 mmol, 6.765 g) in dry DMF (250 mL) was treated with N,N-diisopropylethylamine (104 mmol, 13.442 g) followed by 2-propyl-pentanoic acid chloromethyl ester (88 mmol, 17 g, synthesis described below) at ambient temperature and under exclusion of moisture. The reaction mixture was heated to 65° C. and held, with stirring, at 65° C. for over 16 hours. The solvent was removed by vacuum distillation and the residue was partitioned (2×) between water and ether. The organic phase was separated, dried over magnesium sulfate, filtered, and evaporated to dryness affording about 16 g of crude product as a dense yellow oil. This oil was flash chromatographed on 350 g silica gel. Elution with 8% methanol/ethyl acetate afforded 8.4 g (56%) of the desired product as a colorless solidified wax. MS (ES+): m/e 573 (M+H). The solvent was removed by vacuum distillation the residue was partitioned (2×) between water and ether The organic phase was separated dried over magnesium sulfate filtered evaporated to dryness affording about 16 g of crude product as a dense yellow oil chromatographed on 350 g silica gel Elution with 8% methanol/ethyl acetate

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

Procedure: Para-formaldehyde (1 g) and zinc chloride (catalytic amount) were mixed together at 0° C. 2,2-Di-n-propylacetyl chloride (30 mole, 4.88 g) was added dropwise over 1 hour. The reaction was warmed to ambient temperature, then was heated to 50-55° C. for 6 hours. The reaction mixture continued stirring at room temperature for 16 hours. The reaction mixture was taken up with methylene chloride (5 mL) and flash chromatographed on 150 g silica gel. Elution with 1 to 5% ethyl acetate/hexane gave 3.3 g (58%) of the desired product. was heated to 50-55° C. for 6 hours chromatographed on 150 g silica gel Elution with 1 to 5% ethyl acetate/hexane

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of the starting [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)ethyl]phosphonic acid (26 mmol, 6.765 g) in dry DMF (250 mL) was treated with N,N-diisopropylethylamine (104 mmol, 13.442 g) followed by 2-propyl-pentanoic acid chloromethyl ester (88 mmol, 17 g, synthesis described below) at ambient temperature and under exclusion of moisture. The reaction mixture was heated to 65° C. and held, with stirring, at 65° C. for over 16 hours. The solvent was removed by vacuum distillation and the residue was partitioned (2×) between water and ether. The organic phase was separated, dried over magnesium sulfate, filtered, and evaporated to dryness affording about 16 g of crude product as a dense yellow oil. This oil was flash chromatographed on 350 g silica gel. Elution with 8% methanol/ethyl acetate afforded 8.4 g (56%) of the desired product as a colorless solidified wax. MS (ES+): m/e 573 (M+H). The solvent was removed by vacuum distillation the residue was partitioned (2×) between water and ether The organic phase was separated dried over magnesium sulfate filtered evaporated to dryness affording about 16 g of crude product as a dense yellow oil chromatographed on 350 g silica gel Elution with 8% methanol/ethyl acetate

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

Procedure: Para-formaldehyde (1 g) and zinc chloride (catalytic amount) were mixed together at 0° C. 2,2-Di-n-propylacetyl chloride (30 mole, 4.88 g) was added dropwise over 1 hour. The reaction was warmed to ambient temperature, then was heated to 50-55° C. for 6 hours. The reaction mixture continued stirring at room temperature for 16 hours. The reaction mixture was taken up with methylene chloride (5 mL) and flash chromatographed on 150 g silica gel. Elution with 1 to 5% ethyl acetate/hexane gave 3.3 g (58%) of the desired product. was heated to 50-55° C. for 6 hours chromatographed on 150 g silica gel Elution with 1 to 5% ethyl acetate/hexane

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of the starting [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)ethyl]phosphonic acid (26 mmol, 6.765 g) in dry DMF (250 mL) was treated with N,N-diisopropylethylamine (104 mmol, 13.442 g) followed by 2-propyl-pentanoic acid chloromethyl ester (88 mmol, 17 g, synthesis described below) at ambient temperature and under exclusion of moisture. The reaction mixture was heated to 65° C. and held, with stirring, at 65° C. for over 16 hours. The solvent was removed by vacuum distillation and the residue was partitioned (2×) between water and ether. The organic phase was separated, dried over magnesium sulfate, filtered, and evaporated to dryness affording about 16 g of crude product as a dense yellow oil. This oil was flash chromatographed on 350 g silica gel. Elution with 8% methanol/ethyl acetate afforded 8.4 g (56%) of the desired product as a colorless solidified wax. MS (ES+): m/e 573 (M+H). The solvent was removed by vacuum distillation the residue was partitioned (2×) between water and ether The organic phase was separated dried over magnesium sulfate filtered evaporated to dryness affording about 16 g of crude product as a dense yellow oil chromatographed on 350 g silica gel Elution with 8% methanol/ethyl acetate