2-chloroethyl 2-hydroxypropanoate

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: The efficacy of various enzyme preparations to catalyze the conversion of 0.25 M 2-chloroethyl lactate and 0.25 m isopropyl glycolate in ethyl ether to the title compound was determined after reaction for 24 hr with 0.5 g enzyme per 6.5 mL reaction mixture. Substituting Lipase AK, porcine pancreatic lipase, Lipase MAP10, Protease M, Lipase AP12, or Lipase G for Lipase P30, the relative values for conversion (Lipase P30 =100) were 104, 44, 40, 36, 29 and 26, respectively. In each case substitution of acetonitrile for ethyl ether resulted in a slight reduction in the rate of reaction.

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

Procedure: 2-Chloroethyl lactate (1.91 g, 12.5 mmol) and various amounts of isopropyl glycolate (1.48, 2.22 and 2.95 g; 12.5, 18.8 and 25.0 mmol, respectively) in 25 mL of ethyl ether containing 0.125% tert-butylbenzene were added to 1.75 g Lipase P30 powder and the reaction mixtures were agitated on an orbital shaker (175 RPM) at room temperature for 48 hr. After 48 hr, conversion of 2-chloroethyl lactate to the title compound was estimated (by GC, Method A) to be 30, 38 and 44% with 1.0, 1.5 and 2.0 equivalents of isopropyl glycolate, respectively. The GC peak assigned to the title compound was confirmed by HRMS: calcd for C7H10O5Tms (M--CH3) 247.1001, obsd 247.0990. A portion of one of the reactions was partially purified by flash chromatography (ethyl acetate/hexane, 20/80) to give a mixture of 2-chloroethyl lactate and the title compound. The partially purified mixture was separated by flash chromatography (CH2Cl2 /isopropanol, 99/1) to give the title compound: 1H NMR δ 1.27 (d, 6H, J=6.3 Hz), δ 1.49 (d, 3H, J=7.0 Hz), δ 3.28 (d, 1H, J=4.6 Hz), δ 4.42 (m, 1H), δ 4.60 (d, 1H, J=15.8 Hz),δ 4.71 (d, 1H, J=15.8 Hz), δ]5.09 (m, 1H, J=6.3 Hz); 13C NMR 20.3, 21.7, 61.5, 66.9, 69.6, 166.8, 174.9. the reaction mixtures After 48 hr

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

Procedure: A 6.5 mL aliquot of an ethyl ether solution containing 0.25 M 2-chloroethyl lactate (prepared as described in Example 1a), 0.25 M methyl glycolate, and 0.125% tert-butylbenzene was added to 0.5 g Lipase P30. After mixing for 48 hr at room temperature, the conversion of 2-chloroethyl lactate to the title compound was estimated (by GC, Method A) to be 40%. In identical reactions substituting Lipase AK, Lipase G, Lipase MAP10, Protease M, Lipase AP12, or porcine pancreatic lipase for Lipase P30, the relative values for conversions at 48 hr (Lipase P30 =100) were 101, 90, 44, 43, 32, and 13, respectively. was added to 0.5 g Lipase P30 After mixing for 48 hr at room temperature

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

Procedure: 2-Chloroethyl lactate (19.10 g, 0.125 mol) and methyl glycolate (11.26 g, 0.125 mol) in 250 mL of ethyl ether containing 0.125% tert-butylbenzene was added to 17.5 g Lipase P30 powder in duplicate reactions. The reaction mixtures were agitated on an orbital shaker (175 RPM) at room temperature for 8 hr and an additional equivalent of methyl glycolate was added. After agitation for a further 40 hr, the enzyme powders were removed by filtration and the filtrates were combined and evaporated. The resulting residue was chromatographed by flash chromatography (ethyl acetate/hexane, 22.5/77.5) to give the title compound as an oil (6.00 g, 15%--an approximately equal amount of product was recovered in fractions which also contained methyl glycolate): 1H NMR δ 1.49 (d, 3 H, J=7.0 Hz), δ 3.55 (bs, 1 H), δ 3.78 (s, 3 H), 8 4.43 (q, 1 H, i=6.9 Hz), δ 4.67 (d, 1 H, J=15.9 Hz), δ 4.76 (d, 1 H, J=15.9 Hz); 13C NMR 20.04, 52.09, 60.87, 66.67, 167.63, 174.62; HRMS calcd for C5H6O5Tms (M--CH3) 219.0688, obsd 219.0641. The reaction mixtures After agitation for a further 40 hr the enzyme powders were removed by filtration evaporated The resulting residue was chromatographed by flash chromatography (ethyl acetate/hexane, 22.5/77.5)

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

Procedure: Lactic acid (74 mL of an 85% aqueous solution, 0.84 mol) and freshly distilled 2-chloroethanol (670 mL, 10.0 mol) were refluxed with 400 mL of toluene and 0.4 mL of conc. H2SO4 until one equivalent of H2O was collected in a Dean-Stark trap. The reaction mixture was cooled to room temperature, diluted with ethyl ether, and washed with a NaHCO3 /NaCl solution. The organic phase was dried with MgSO4, solvent was removed under reduced pressure, and the residue was distilled at 10 mm Hg. A fraction recovered at 95°-100° C./10 mm Hg was redistilled to give 2-chloroethyl lactate as a clear colorless liquid (76.7 g, 60%): b.p. 95° C./10 mm Hg; 1H NMR δ 1.46 (d, 3 H, J=6.9 Hz), δ 2.95 (bs, 1 H), δ 3.72 (t, 2 H, J=5.6 Hz), δ 4.35 (q, 1 H, J=6.9 Hz), δ 4.44 (m, 2 H); 13C NMR20.4, 41.2, 64.8, 66.8, 175.2 ppm; HRMS calcd for C4H5ClO3Tms (M--CH3) 209.0401, obsd 209.0392. was collected in a Dean-Stark trap diluted with ethyl ether washed with a NaHCO3 /NaCl solution The organic phase was dried with MgSO4, solvent was removed under reduced pressure the residue was distilled at 10 mm Hg A fraction recovered at 95°-100° C./10 mm Hg was redistilled

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

Procedure: The efficacy of various enzyme preparations to catalyze the conversion of 0.25M 2-chloroethyl lactate and 0.25M isopropyl glycolate in ethyl ether to the title compound was determined after reaction for 24 hr with 0.5 g enzyme per 6.5 mL reaction mixture. Substituting Lipase AK, porcine pancreatic lipase, Lipase MAP10, Protease M, Lipase AP12, or Lipase G for Lipase P30, the relative values for conversion (Lipase P30=100) were 104, 44, 40, 36, 29 and 26, respectively. In each case substitution of acetonitrile for ethyl ether resulted in a slight reduction in the rate of reaction.

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

Procedure: 2-Chloroethyl lactate (1.91 g, 12.5 mmol) and various amounts of isopropyl glycolate (1.48, 2.22 and 2.95 g; 12.5, 18.8 and 25.0 mmol, respectively) in 25 mL of ethyl ether containing 0.125% tert-butylbenzene were added to 1.75 g Lipase P30 powder and the reaction mixtures were agitated on an orbital shaker (175 RPM) at room temperature for 48 hr. After 48 hr, conversion of 2-chloroethyl lactate to the title compound was estimated (by GC, Method A) to be 30, 38 and 44% with 1.0, 1.5 and 2.0 equivalents of isopropyl glycolate, respectively. The GC peak assigned to the title compound was confirmed by HRMS: calcd for C7H10O5Tms (M-CH3) 247.1001, obsd 247.0990. A portion of one of the reactions was partially purified by flash chromatography (ethyl acetate/hexane, 20/80) to give a mixture of 2-chloroethyl lactate and the title compound. The partially purified mixture was separated by flash chromatography (CH2Cl2 /isopropanol, 99/1) to give the title compound: 1H NMR δ1.27 (d, 6H, J=6.3 Hz), δ1.49 (d, 3H, J=7.0 Hz), δ3.28 (d, 1H, J=4.6 Hz), δ4.42 (m, 1H), δ4.60 (d, 1H, J=15.8 Hz),δ4.71 (d, 1H, J=15.8 Hz), δ5.09 (m, 1H, J=6.3 Hz); 13C NMR 20.3, 21.7, 61.5, 66.9, 69.6, 166.8, 174.9. the reaction mixtures After 48 hr

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

Procedure: A 6.5 mL aliquot of an ethyl ether solution containing 0.25M 2-chloroethyl lactate (prepared as described in Example 1a), 0.25M methyl glycolate, and 0.125% tert-butylbenzene was added to 0.5 g Lipase P30. After mixing for 48 hr at room temperature, the conversion of 2-chloroethyl lactate to the title compound was estimated (by GC, Method A) to be 40%. In identical reactions substituting Lipase AK, Lipase G, Lipase MAP10, Protease M, Lipase AP12, or porcine pancreatic lipase for Lipase P30, the relative values for conversions at 48 hr (Lipase P30=100) were 101, 90, 44, 43, 32, and 13, respectively. was added to 0.5 g Lipase P30 After mixing for 48 hr at room temperature