methyl 2-phenoxyacetate

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

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

Conditions: temp:28.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 100 mg sample of [(2R,3S),(2S,3R)]-3-amino- <2-[2-(2-furanyl)ethyl]-4-oxo-1-azetidine acetic acid, methyl ester oxalate salt and a 135 mg sample of methyl phenoxyacetate were added to 0.lM phosphate buffer (100 ml final volume) and adjusted to pH=6.0 with lN KOH. Milli-Q™ H2O washed Sclavo penicillin G amidase (40 I.U. of enzyme per gram of substrate) was then added to the reaction mixture and the pH of reaction mixture was maintained at 6.0 and temperature at 28° C. for 8 hours. The reaction mixture was then filtered to remove the immobilized enzyme and extracted two times with ethyl acetate. The organic extracts were then dried over anhydrous sodium sulfate and concentrated to dryness in vacuo. The title compound was then isolated by column chromatography from this residue using a Kiesegel 60™ column eluted with toluene/ethyl acetate (70/30). Yield: 13%. the pH of reaction mixture The reaction mixture was then filtered to remove the immobilized enzyme extracted two times with ethyl acetate The organic extracts were then dried over anhydrous sodium sulfate concentrated to dryness in vacuo

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

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

Procedure: Aluminium chloride (33.35 g) was added portionwise to a stirred cooled (<0° C.) solution of methyl phenoxyacetate (14.46 ml) and 3-chloropropionyl chloride (9.55 ml) in dichloromethane (500 ml). After the addition the ice-bath was removed and the mixture stirred for 1 hour when it was poured into ice-water (500 ml). The organic phase was separated and the aqueous portion extracted two times with dichloromethane. The combined dichloromethane extracts were washed with water, then brine and dried (MgSO4). The residue, after removal of the solvent in vacuo and trituration with ether gave methyl 4-[3-chloropropanoyl]phenoxyacetate, 22.3 g, as a solid: m.p. 89°-90° C.; NMR (d6DMSO) δ 7.95(2H,d), 7.05(2H,d), 4.92(2H,s), 3.91(2H,t), 3.71(3H,s), 3.49(2H,t); m/e 257(M+H)+ ; calculated for C12H13ClO4 : C, 56.1; H, 5.0. found: C, 55.8; H, 5.1%. was removed was poured into ice-water (500 ml) The organic phase was separated the aqueous portion extracted two times with dichloromethane The combined dichloromethane extracts were washed with water brine and dried (MgSO4) The residue, after removal of the solvent in vacuo and trituration with ether

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

Procedure: Aluminium chloride (33.35 g) was added portionwise to a stirred cooled (<0° C.) solution of methyl phenoxyacetate (14.46 ml) and 3-chloropropionyl chloride (9.55 ml) in dichloromethane (500 ml). After the addition the ice-bath was removed and the mixture stirred for 1 hour when it was poured into ice-water (500 ml). The organic phase was separated and the aqueous portion extracted two times with dichloromethane. The combined dichloromethane extracts were washed with water, then brine and dried (MgSO4). The residue, after removal of the solvent in vacuo and trituration with ether gave methyl 4-[3-chloropropanoyl]phenoxyacetate, 22.3 g, as a solid: m.p. 89°-90° C.; NMR (d6DMSO) δ 7.95(2H,d), 7.05(2H,d), 4.92(2H,s), 3.91(2H,t), 3.71(3H,s), 3.49(2H,t); m/e 257(M+H)+ ; calculated for C12H13ClO4 : C, 56.1; H, 5.0. found: C, 55.8; H, 5.1%. was removed was poured into ice-water (500 ml) The organic phase was separated the aqueous portion extracted two times with dichloromethane The combined dichloromethane extracts were washed with water brine and dried (MgSO4) The residue, after removal of the solvent in vacuo and trituration with ether

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dimethyl methylphosphonate (18 ml, 0.166 mol) was addded to anhydrous THF (150 ml) under argon atmosphere and cooled to -78° C. After 20 min. a solution of n-butyl lithium in hexane (1.59N, 108.8 ml, 0.173 mmol) was added to the mixture. After being stirred for 30 min. a solution of methyl phenoxyacetate (10 ml, 0.069 mmol) in 10 ml of anhydrous THF was added, and the reaction mixture was stirred successively for 30 min. at -78° C. and for 30 min. at room temperature, and acidified with acetic acid. After confirming a weakly acidic pH of the solution thus obtained, THF was distilled out. Water (50 ml) was added to the residue, and the resulting mixture was extracted with ethyl acetate (150 ml×3). The combined organic layers were washed with 100 ml of water and with 100 ml of brine, dried over anhydrous sodium sulfate, and concentrated. The oily product was distilled under reduced pressure to afford dimethyl 2-oxo-3-phenoxypropylphosphonate (14.65 g, 0.057 mol, yield: 82.3%). B.p.: 145°-147° C./0.1 mmHg. The product was identified by the following data. was added thus obtained THF was distilled out Water (50 ml) was added to the residue the resulting mixture was extracted with ethyl acetate (150 ml×3) The combined organic layers were washed with 100 ml of water and with 100 ml of brine dried over anhydrous sodium sulfate concentrated The oily product was distilled under reduced pressure

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

Procedure: Aluminium chloride (33.35 g) was added portionwise to a stirred cooled (<0° C.) solution of methyl phenoxyacetate (14.46 ml) and 3-chloropropionyl chloride (9.55 ml) in dichloromethane (500 ml). After the addition the ice-bath was removed and the mixture stirred for 1 hour when it was poured into ice-water (500 ml). The organic phase was separated and the aqueous portion extracted two times with dichloromethane. The combined dichloromethane extracts were washed with water, then brine and dried (MgSO4). The residue, after removal of the solvent in vacuo and trituration with ether gave methyl 4-[3-chloropropanoyl]phenoxyacetate, 22.3 g, as a solid: m.p. 89°-90° C.; NMR (d6DMSO) δ7.95(2H,d), 7.05(2H,d), 4.92(2H,s), 3.91(2H,t), 3.71(3H,s), 3.49(2H t); m/e 257(M+H)+ ; calculated for C12H13ClO4 : C, 56.1; H, 5.0. found: C, 55.8; H, 5.1%. was removed was poured into ice-water (500 ml) The organic phase was separated the aqueous portion extracted two times with dichloromethane The combined dichloromethane extracts were washed with water brine and dried (MgSO4) The residue, after removal of the solvent in vacuo and trituration with ether

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

Procedure: Aluminium chloride (33.35 g) was added portionwise to a stirred cooled (<0° C.) solution of methyl phenoxyacetate (14.46 ml) and 3-chloropropionyl chloride (9.55 ml) in dichloromethane (500 ml). After the addition the ice-bath was removed and the mixture stirred for 1 hour when it was poured into ice-water (500 ml). The organic phase was separated and the aqueous portion extracted two times with dichloromethane. The combined dichloromethane extracts were washed with water, then brine and dried (MgSO4). The residue, after removal of the solvent in vacuo and trituration with ether gave methyl 4-[3-chloropropanoyl]phenoxyacetate, 22.3 g, as a solid: m.p. 89°-90° C.; NMR (d6DMSO) δ7.95(2H,d), 7.05(2H,d), 4.92(2H,s), 3.91(2H,t), 3.71(3H,s) 3.49(2H,t); m/e 257(M+H)+ ; calculated for C12H13C104 : C, 56.1; H, 5.0. found: C, 55.8; H, 5.1%. was removed was poured into ice-water (500 ml) The organic phase was separated the aqueous portion extracted two times with dichloromethane The combined dichloromethane extracts were washed with water brine and dried (MgSO4) The residue, after removal of the solvent in vacuo and trituration with ether

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

Procedure: Aluminium chloride (33.35 g) was added portionwise to a stirred cooled (<0° C.) solution of methyl phenoxyacetate (14.46 ml) and 3-chloropropionyl chloride (9.55 ml) in dichloromethane (500 ml). After the addition the ice-bath was removed and the mixture stirred for 1 hour when it was poured into ice-water (500 ml). The organic phase was separated and the aqueous portion extracted two times with dichloromethane. The combined dichloromethane extracts were washed with water, then brine and dried (MgSO4). The residue, after removal of the solvent in vacuo and trituration with ether gave methyl 4-[3-chloropropanoyl]phenoxyacetate, 22.3 g, as a solid: m.p. 89°-90° C.; NMR (d6DMSO) δ7.95(2H,d), 7.05(2H,d), 4.92(2H,s), 3.91(2H,t), 3.71(3H,s) 3.49(2H,t); m/e 257(M+H)+ ; calculated for C12H13C104 : C, 56.1; H, 5.0. found: C, 55.8; H, 5.1%. was removed was poured into ice-water (500 ml) The organic phase was separated the aqueous portion extracted two times with dichloromethane The combined dichloromethane extracts were washed with water brine and dried (MgSO4) The residue, after removal of the solvent in vacuo and trituration with ether

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an oven-dried round bottom flask was added anhydrous AlCl3 (24.1 g, 0.18 mol), which was subsequently purged with Ar. Methylene chloride (10 mL) was added via syringe and the resulting slurry was cooled to 0° C. in an ice bath. The isobutryl chloride (6.9 mL, 6.6×10−2 mol) was added dropwise via syringe. The methyl phenoxy acetate (8.7 mL, 6.0×10−2 mol) was added dropwise via syringe. The reaction was stirred until deemed complete by thin layer chromatography (TLC) (25% ethyl acetate in hexane) (approximately 2 h). The reaction mixture was poured slowly into a mixture of ice (100 g) and concentrated HCl (40 mL). The organic layer was separated and the organic layer extracted with methylene chloride (3×100 mL). The combined organic layers were washed with water (3×100 mL) and dried over MgSO4. The solvent was removed in vacuo to reveal 14 g of a white, crystalline solid (quantitative yield). 1H NMR (300 NMR, CDCl3) δ7.97 (2H, d, J=8.9 Hz), 6.96 (2H, J=8.9 Hz), 4.71 (2H, s), 3.82 (3H, s), 3.51 (1H, septet, J=6.8 Hz), 1.22 (6H, d, J=6.8 Hz). was subsequently purged with Ar Methylene chloride (10 mL) was added via syringe The organic layer was separated the organic layer extracted with methylene chloride (3×100 mL) The combined organic layers were washed with water (3×100 mL) dried over MgSO4 The solvent was removed in vacuo

Conditions: temp:28.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 100 mg sample of [(2R,3S),(2S,3R)]-3-amino- <2-[2-(2-furanyl)ethyl]-4-oxo-1-azetidine acetic acid, methyl ester oxalate salt and a 135 mg sample of methyl phenoxyacetate were added to 0.lM phosphate buffer (100 ml final volume) and adjusted to pH=6.0 with lN KOH. Milli-Q™ H2O washed Sclavo penicillin G amidase (40 I.U. of enzyme per gram of substrate) was then added to the reaction mixture and the pH of reaction mixture was maintained at 6.0 and temperature at 28° C. for 8 hours. The reaction mixture was then filtered to remove the immobilized enzyme and extracted two times with ethyl acetate. The organic extracts were then dried over anhydrous sodium sulfate and concentrated to dryness in vacuo. The title compound was then isolated by column chromatography from this residue using a Kiesegel 60™ column eluted with toluene/ethyl acetate (70/30). Yield: 13%. the pH of reaction mixture The reaction mixture was then filtered to remove the immobilized enzyme extracted two times with ethyl acetate The organic extracts were then dried over anhydrous sodium sulfate concentrated to dryness in vacuo