ethyl 2-(2-chlorophenoxy)acetate

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:

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-chlorophenol (2.06 mL, 19.9 mmol) in DMF (40 mL) is added potassium carbonate (3.03 g, 21.9 mmol) and ethyl bromoacetate (2.3 mL, 20.7 mmol), and the mixture is stirred at 80° C. for 18 h. Et2O is added, and the mixture is washed with water, brine, dried (MgSO4), and filtered. The filtrate is evaporated, and the residue is purified by chromatography in silica gel; elution with EtOAc:dichloromethane:hexane (10:5:85) gives 4.17 g of the product 465. 1H NMR (CDCl3) δ 7.38 (d, 1H), 7.21 (t, 1H), 6.92 (t, 1H), 6.84 (d, 1H), 4.70 (s, 2H), 4.27 (q, 2H), 1.29 (t, 3H); MS: m/z 215, 217 (M++1). the mixture is washed with water, brine dried (MgSO4) filtered The filtrate is evaporated the residue is purified by chromatography in silica gel elution with EtOAc:dichloromethane:hexane (10:5:85)

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

Procedure: To a stirred solution of ethyl 2-chlorophenoxyacetate (32.0 g, 149 mmol) in dichloromethane (75 mL) at ambient temperature under nitrogen was added succinic anhydride (22.4 g, 224 mmol). The reaction mixture was cooled in ice-water and to this was added portion wise aluminum trichloride (59.6 g, 447 mmol), whilst maintaining the temperature below 20° C. The reaction mixture was then allowed to stir at ambient temperature for 20 minutes and was then heated to reflux and stirred at this temperature for 3 hours. The reaction mixture was allowed to cool to ambient temperature, then poured into a mixture of ice, water (200 ml) and HCl (10 N, 100 ml). The two phase system was separated and the aqueous layer was extracted with ethyl acetate (5×100 mL). All organic layers were then combined and washed with water (2×100 mL), dried over Na2SO4, and concentrated under reduced pressure to give an orange oily solid. Hexane (300 mL) was added, and after standing at ambient temperature for 1 hour, the precipitate was filtered off and re-crystallized from ethyl acetate/hexane to give 9 as a light yellow powder (21.5 g, 46% yield, 98% pure by LCMS and 1H NMR), 1H NMR (400 MHz; CDCl3): δ 7.79 (m, 1H); 7.66 (m, 1H); 6.79 (m, 1H); 4.90 (s, 2H); 4.12 (q, 2H); 2.82 (m, 2H); 2.42 (m, 2H); 1.30 (t, 3H). whilst maintaining the temperature below 20° C was then heated to reflux stirred at this temperature for 3 hours to cool to ambient temperature The two phase system was separated the aqueous layer was extracted with ethyl acetate (5×100 mL) washed with water (2×100 mL) dried over Na2SO4 concentrated under reduced pressure to give an orange oily solid after standing at ambient temperature for 1 hour the precipitate was filtered off re-crystallized from ethyl acetate/hexane

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

Procedure: To a stirred solution of 2-chlorophenol (6, 20.0 g, 156 mmol) in acetone (300 mL) under nitrogen at ambient temperature were added potassium carbonate (23.7 g, 171 mmol) and ethyl bromoacetate (7, 26.0 g, 156 mmol). The reaction mixture was then heated to reflux and stirred at this temperature under nitrogen for 7 hours. After cooling to ambient temperature, the reaction mixture was filtered to remove insolubles. The filtrate was then concentrated under reduced pressure to give 8 as highly viscous, light yellow oil (32.0 g, 95% yield, 95% pure by LCMS and 1H NMR), 1H NMR (400 MHz; CDCl3): δ 7.16 (m, 1H); 7.03 (m, 1H); 6.76 (m, 1H); 6.71 (m, 1H); 4.90 (s, 2H); 4.12 (q, 2H); 1.33 (t, 3H). The reaction mixture was then heated to reflux the reaction mixture was filtered to remove insolubles The filtrate was then concentrated under reduced pressure to give 8 as highly viscous, light yellow oil (32.0 g, 95% yield, 95% pure by LCMS and 1H NMR), 1H NMR (400 MHz; CDCl3): δ 7.16 (m, 1H); 7.03 (m, 1H); 6.76 (m, 1H); 6.71 (m, 1H); 4.90 (s, 2H); 4.12 (q, 2H); 1.33 (t, 3H)

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-chlorophenol (2.06 mL, 19.9 mmol) in DMF (40 mL) is added potassium carbonate (3.03 g, 21.9 mmol) and ethyl bromoacetate (2.3 mL, 20.7 mmol), and the mixture is stirred at 80° C. for 18 h. Et2O is added, and the mixture is washed with water, brine, dried (MgSO4), and filtered. The filtrate is evaporated, and the residue is purified by chromatography in silica gel; elution with EtOAc:dichloromethane:hexane (10:5:85) gives 4.17 g of the product 465. 1H NMR (CDCl3) δ 7.38 (d, 1H), 7.21 (t, 1H), 6.92 (t, 1H), 6.84 (d, 1H), 4.70 (s, 2H), 4.27 (q, 2H), 1.29 (t, 3H); MS: m/z 215, 217 (M++1). the mixture is washed with water, brine dried (MgSO4) filtered The filtrate is evaporated the residue is purified by chromatography in silica gel elution with EtOAc:dichloromethane:hexane (10:5:85)

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

Procedure: To a stirred solution of ethyl 2-chlorophenoxyacetate (32.0 g, 149 mmol) in dichloromethane (75 mL) at ambient temperature under nitrogen was added succinic anhydride (22.4 g, 224 mmol). The reaction mixture was cooled in ice-water and to this was added portion wise aluminum trichloride (59.6 g, 447 mmol), whilst maintaining the temperature below 20° C. The reaction mixture was then allowed to stir at ambient temperature for 20 minutes and was then heated to reflux and stirred at this temperature for 3 hours. The reaction mixture was allowed to cool to ambient temperature, then poured into a mixture of ice, water (200 ml) and HCl (10 N, 100 ml). The two phase system was separated and the aqueous layer was extracted with ethyl acetate (5×100 mL). All organic layers were then combined and washed with water (2×100 mL), dried over Na2SO4, and concentrated under reduced pressure to give an orange oily solid. Hexane (300 mL) was added, and after standing at ambient temperature for 1 hour, the precipitate was filtered off and re-crystallized from ethyl acetate/hexane to give 9 as a light yellow powder (21.5 g, 46% yield, 98% pure by LCMS and 1H NMR), 1H NMR (400 MHz; CDCl3): δ 7.79 (m, 1H); 7.66 (m, 1H); 6.79 (m, 1H); 4.90 (s, 2H); 4.12 (q, 2H); 2.82 (m, 2H); 2.42 (m, 2H); 1.30 (t, 3H). whilst maintaining the temperature below 20° C was then heated to reflux stirred at this temperature for 3 hours to cool to ambient temperature The two phase system was separated the aqueous layer was extracted with ethyl acetate (5×100 mL) washed with water (2×100 mL) dried over Na2SO4 concentrated under reduced pressure to give an orange oily solid after standing at ambient temperature for 1 hour the precipitate was filtered off re-crystallized from ethyl acetate/hexane